Method and apparatus for gastrointestinal tract ablation for treatment of obesity

ABSTRACT

Devices and methods for ablating tissue in the wall of various organs of the gastrointestinal tract of a patient in order to cure or ameliorate metabolic pathophysiological conditions such as obesity, insulin resistance, or type 2 diabetes mellitus are provided. Ablational treatment of target areas may be fractional or partial, rendering a post-treatment portion of target tissue ablated and another portion that is substantially intact. Fractional ablation is achieved by controlling the delivery of ablational energy across the surface area being treated, and controlling the depth of energy penetration into tissue. Surface area control of energy delivery may controlled by the spatial pattern of distributed ablation elements or by the selective activation of a subset of a dense pattern of ablation elements. Embodiments of the device include an ablational electrode array that spans 360 degrees and an array that spans an arc of less than 360 degrees.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent ApplicationNo. 60/916,248 entitled “Method and Apparatus for Treating Obesity” byUtley, et al., as filed on May 4, 2007, to U.S. Provisional PatentApplication No. 60/958,543 entitled “Non-Barrett's Mucosal Ablation andTissue Tightening Indications Related to Obesity” by Utley, as filed onJul. 6, 2007, and to U.S. Provisional Patent Application No. 60/958,562entitled “Non-Barrett's Mucosal Ablation Disease Targets”, as filed onJul. 6, 2007.

This application is also related to, and incorporates in entiretycommonly assigned U.S. patent application Ser. No. 10/370,645 entitled“Method of treating abnormal tissue in the human esophagus”, filed onFeb. 19, 2003, and published as US 2003/0158550 on Aug. 21, 2003, andthis present application is also a continuation-in-part of U.S. patentapplication Ser. No. 11/286,444 entitled “Precision Ablating Method”,filed on Nov. 23, 2005, and published as US 2007/0118106 on May 24,2007. Further, each of the following commonly assigned United StatesPatent Applications are incorporated herein by reference in itsentirety: patent application Ser. No. 10/291,862 titled “Systems andMethods for Treating Obesity and Other Gastrointestinal Conditions,”patent application Ser. No. 10/370,645 titled “Method of TreatingAbnormal Tissue In The Human Esophagus,” patent application Ser. No.11/286,257 titled “Precision Ablating Device,” patent application Ser.No. 11/275,244 titled “Auto-aligning ablating device and method of use,”patent application Ser. No. 11/286,444 titled “Precision AblatingDevice,” patent application Ser. No. 11/420,712 titled “System forTissue Ablation,” patent application Ser. No. 11/420,714 titled “Methodfor Cryogenic Tissue Ablation,” patent application Ser. No. 11/420,719titled “Method for Vacuum-Assisted Tissue Ablation,” patent applicationSer. No. 11/420,722 titled “Method for Tissue Ablation,” patentapplication Ser. No. 11/469,816 titled “Surgical instruments andtechniques for treating gastro-esophageal reflux disease.” Thisapplication further incorporates in entirety U.S. patent applicationSer. No. 10/291,862, filed on Nov. 8, 2002 entitled “Systems and methodsfor treating obesity and other gastrointestinal conditions, andpublished on May 13, 2004 as US 2004/0089313, and U.S. Pat. No.7,326,207, entitled “surgical weight control device”, which issued onFeb. 5, 2008.

INCORPORATION BY REFERENCE

All publications, patents and patent applications mentioned in thisspecification are herein incorporated by reference to the same extent asif each individual publication, patent or patent application wasspecifically and individually indicated to be incorporated by reference.

FIELD OF THE INVENTION

The invention relates to medical devices and methods for the use thereoffor the ablating of tissue in the gastrointestinal tract for thetreatment of metabolic disease and obesity.

BACKGROUND OF THE INVENTION

Gastric bypass surgical procedures whose original intended result was tocause weight loss by virtue of a major decrease in nutrient absorption,in addition to a significant degree of success toward that end, havealso resulted in the amelioration or elimination of Type 2 diabetesmellitus in 70-80% of post-operative patients. The prevalence and theextremely quick time course of this effect in reducing diabetes was notgenerally anticipated, nor can it be satisfactorily explained by weightloss alone.

It has been hypothesized (Rubino and Gagner, “Potential of surgery forcuring type 2 diabetes mellitus”, Annals of Surgery (2002) 236 (5),554-559, Rubino and Marescaux, “Effect of duodenal-jejunal exclusion ina non-obese animal model of type 2 diabetes: a new perspective for anold disease” Annals of Surgery (2004) 240(2): 389-391) that the removalor functional compromise of endocrine and neural cells within theepithelium of the intestinal tract, the small bowel in particular, whichnormally respond to the passage of nutrient flow were at least partiallyresponsible for the decrease in diabetes symptoms in these treatedpatients. Various hormones secreted by endocrine cells in the duodenumand jejunum are collectively known as incretins, and includegastroinhibitory peptide (GIP), glucagon-like peptide (GLP-1), andinsulin-like growth factor (IGF-1). The passage or presence of nutrientsin the intestine stimulate the release of these hormones which have abroadly stimulatory effect on insulin secretion by the pancreas, and onenhancing the effectiveness of insulin on its targets. This relationshipmakes sense in that insulin helps the body to move glucose and aminoacids from the blood stream into tissues, and thus the incretins preparethe body to receive nutrients that are sensed within the intestine evenbefore the nutrients move into the bloodstream. In the pathogenesis ofdiabetes, however, there is an excessive amount of insulin secreted, andin response the cells responsive to insulin become overly stimulated andcompensate by becoming insulin resistant. The patient with type 2diabetes thus has a surfeit of insulin, but physiologically acts as ifthere is an insulin deficit. Accordingly, insulin levels and bloodglucose levels are high. Whether the initial disturbance is diabetes oran over consumption of calories independent of diabetes, the end resultis similar, and most obese patients are have type 2(non-insulin-dependent) diabetes mellitus.

Other factors may be involved in the striking anti-diabetic response tobariatric surgery, such as an increase in the levels of anti-incretinfactors, which would favor the effectiveness of insulin action.Additionally, the stomach wall itself is a source of hormones such ascholecystokinin (CCK), gastrin, and ghrelin, all of which play variousroles in the handling of nutrients, the activity of other hormones,particularly pancreatic hormones, and on the sensation of satiety, whichhas further neural and behavioral consequences. Additionally, theintestine is well innervated with chemically sensitive receptors thatrespond to the nutrients in the stomach and intestine, and mechanicallysensitive cells that respond to the volume of material in the gut andthe state of smooth muscle in the intestinal wall.

Bariatric by-pass surgeries have thus been remarkably successful indecreasing nutrient intake and nutrient absorption, and have had furtherbeneficial effects that enhance their anti-obesity effect with whatappears to be a related but separable anti-diabetic effect. Surgeriessuch as these, however are extremely costly for the health care systemas whole, and carry substantial risk of surgical morbidity andmortality. Even advocates of the use of bariatric surgery for obesityare cautious in recommending surgery as a treatment for diabetes.Clearly, however, diabetes is a major and growing public health problem,and interventions that would bring any of the remarkable effectivenessof bypass surgery but with decreased associated costs and risks would bea highly desirable addition to the currently available treatments formetabolic conditions and diseases such as morbid obesity, metabolicsyndrome, and type 2 diabetes.

SUMMARY OF THE INVENTION

Embodiments of the invention include a system and methods of using thedevices to ablate tissue in the wall of luminal organs of thegastrointestinal tract of a patient pathophysiological metaboliccondition toward the end of alleviating or curing that condition. Themethod of ablationally treating a target area in gastrointestinal tractwall includes delivering radiofrequency energy from a non-penetratingelectrode pattern on an ablation structure to the tissue surface withinthe target area, the target area being a contiguous radial portion ofthe gastrointestinal tract. The method further includes controlling thedelivery of radiofrequency energy into tissue in three dimensions:controlling energy delivery across the surface area of tissue within thetarget area, and controlling delivery into the depth of tissue withinthe target area such that some volume portion of the tissue is ablatedand some volume portion of the tissue is not ablated. Embodiments ofthis type of ablation may be understood as a fractional ablation or apartial ablation within a contiguous target or treatment area, as such,the post-ablationally-treated area of tissue has a mixed pattern ofaffected tissue and areas of substantially unaffected tissue.

Controlling the delivery of radiofrequency energy across the surfacearea of tissue within the target area includes delivering sufficientradiofrequency energy to achieve ablation in one portion of the targettissue surface area to achieve ablation, while at the same time,delivering insufficient radiofrequency energy to another portion of thetissue surface area to achieve ablation. Controlling the delivery ofradiofrequency energy into the depth of the tissue includes controllingthe delivery of radiofrequency energy inwardly from the tissue surfacesuch that sufficient energy to achieve ablation is delivered to sometissue layers and insufficient energy is delivered to other layers toachieve ablation.

In some embodiments of the method, controlling the fraction of thetarget area surface that receives sufficient radiofrequency energy toachieve ablation includes configuring the electrode pattern such thatsome spacing between electrodes is sufficiently close to allowconveyance of a given level of energy sufficient to ablate and otherspacing between electrodes is insufficiently close to allow conveyanceof that level of energy sufficient to ablate.

In other embodiments of the method, controlling the fraction of thetarget area surface that receives sufficient radiofrequency energy toachieve ablation includes operating the electrode pattern such that theenergy delivered between some electrodes is sufficient to ablate andenergy sufficient to ablate is not delivered between some electrodes.The electrodes in this pattern are typically distributed at a higherdensity than in embodiments, as above, where inter-electrode spacingcontrols the fractional distribution of ablated and non-ablated tissue.

In various embodiments, controlling the delivery of energy into inwardlyfrom the surface of the tissue consists of ablating some portion oftissue within the epithelial layer; in other embodiments it consists ofablating some portion of tissue within the epithelial layer and thelamina propria; in other embodiments, it consists of ablating someportion of tissue within the epithelial layer, the lamina propria, andthe muscularis mucosae; in other embodiments, it consists of ablatingsome portion of tissue within the epithelial layer, the lamina propria,the muscularis mucosae, and the submucosa; and in still otherembodiments, it consists of ablating some portion of tissue within theepithelial layer, the lamina propria, the muscularis mucosae, thesubmucosa, and the muscularis propria. In none of the embodiments, isenergy delivered through the wall to reach the level of the serosa.

In various embodiments of the method, the pathophysiological metaboliccondition being addressed by the ablational treatment may include anyone or more of type 2 diabetes, insulin resistance, obesity, ormetabolic syndrome. These embodiments may further include restoring thepathophysiological metabolic condition of the patient toward a normalmetabolic condition. Restoring these various metabolic conditions towarda more normal metabolic condition may be reflected in such indicators asdecreasing absorption of nutrients, decreasing blood glucose levels,decreasing blood insulin levels, decreasing insulin resistance,decreasing body weight, or decreasing body mass index.

In various embodiments of the method, the ablation target area mayincludes cells that support or promote the secretion of insulin in thepatient, and wherein upon receiving transmitted energy from the ablationstructure are rendered at least partially dysfunctional. In some ofthese embodiments, the cells supporting the effect insulin are endocrinecells; in some embodiments, the cells supporting the effect of insulinare nerve cells.

In some embodiments of the method, the ablation target area includescells that support or promote the response of the patient to insulin,and wherein upon receiving transmitted energy from the ablationstructure are rendered at least partially dysfunctional. In someembodiments, supporting the response to insulin includes any ofpromoting the greater effectiveness of secreted insulin or decreasingthe effect of agents that have an anti-insulin effect. In someembodiments, the cells supporting the effect insulin are endocrinecells. In some embodiments, the cells supporting the effect of insulinare nerve cells.

In various embodiments of the method, the ablation target area islocated in the gastric antrum; in some embodiments, the target area islocated in the pylorus; in some embodiments of the method, the targetarea is located in the small intestine, such as in the duodenum or thejejunum.

In various embodiments of the method, controlling the delivery ofradiofrequency energy across the tissue surface within the ablationtarget area and into the depth of tissue within the target area allowsachievement of a partial or fractional ablation in tissue layers of thegastrointestinal tract. Thus, in some embodiments, the ablation targetarea where partial ablation is created is in the epithelial layer of thegastric antrum; in some embodiments, the target area is in epitheliallayer of the small intestine, such as in the duodenum or jejunum. Invarious embodiments of the method, partial ablation in the epitheliallayer slows the rate of nutrient absorption through the epitheliallayer. In other embodiments, the ablation target area where partialablation is created includes the muscularis of the gastric antrum, wheresuch ablation causes a slowing of gastric emptying. In otherembodiments, the target area for partial ablation includes themuscularis of the pyloris, where such ablation causes a slowing ofgastric emptying. And in still other embodiments, the target area forpartial ablation includes the muscularis of the duodenum causing aslowing of gastric emptying.

In various embodiments of the method, the ablation has a permanenteffect on the function of the target area, while in other embodiments,the ablation has a transient effect on the function of the target area.When the effect is transient, the effect may have a duration that rangesfrom a period of about one day to about one year. During the time whenthe function of the target region is transiently affected, the methodmay further include evaluating the patient for a beneficial therapeuticeffect of the ablation. In some embodiments that are transient and abeneficial therapeutic effect is demonstrated, the method may furtherinclude repeating the ablation of the target region. In the event of arepeated ablation, the ablation may be performed as either a secondtransient ablation, or performed to be a permanent ablation.

In some embodiments of the method, the ablational electrode pattern isconfigured circumferentially through 360 degrees around the ablationstructure. In other embodiments that make use of a 360 degree ablationstructure, the method may include transmitting energy from the ablationstructure asymmetrically through the 360 degree circumference such thatablation is focused within an arc of less that 360 degrees. In otherembodiments, the electrode pattern is configured circumferentiallythrough an arc of less than 360 degrees around the ablation structure,such arc, by way example, spanning about 90 degrees or about 180degrees.

Some embodiments of the method may further include evaluating the targetarea at a point in time after delivering energy to the target area inorder to determine the status of the area. In some embodiments,evaluating step occurs in close time proximity after the delivery ofenergy, to evaluate the immediate post-treatment status of the site. Inother embodiments, the evaluating step may occur at least one day afterthe delivery of energy, and in fact, may occur at any length of timeafter the ablational procedure.

In some embodiments, the step of delivering energy is performed one ormore times during an ablational procedure. In other embodiments, theablational procedure may be performed more than once during separatetreatment sessions.

In some embodiments, the method of may include deriving energy fortransmitting from an energy source that is controlled by a controlsystem; and the energy source may be a generator. By way of the controlsystem, the method may include feedback that control the energytransmission so as to provide a controlled level of any of a specificpower, power density, energy, energy density, circuit impedance, ortissue temperature.

In addition to the various method steps summarized above, the method mayfurther include advancing an ablation structure into the alimentarycanal, the non-penetrating electrode pattern on the structure, thestructure supported on an instrument, positioning the ablation structureadjacent to the target area; and moving the ablation structure towardthe surface of the target area to make therapeutic contact on the targetarea prior to delivering energy. In the context of these method steps,the moving step may include any of inflating a balloon member, expandinga deflection member, moving a deflection member, or expanding anexpandable member. The method may also further including aposition-locking step following the moving step, in order to secure atherapeutic contact. In one example, the position-locking step mayinclude developing suction between the structure and the ablation site.Prior to the positioning step, the method may still further include anevaluating step in order to determine the status of the target area.

Embodiments of the method further include evaluating the target areaprior to the positioning step, in order to determine the status of thetarget area. Also, when multiple target areas are being treated, themethod may include the positioning, moving, and transmitting energysteps to a first target area, and the further include the positioning,moving, and transmitting energy steps to another target area withoutremoving the ablation structure from the patient.

Embodiments of the invention include an ablation system with anelectrode pattern that has a plurality of electrodes; a longitudinalsupport member supporting the electrode pattern; a generator coupled tothe plurality of electrodes; and a computer controller in communicationwith the generator. The controller has programming to direct thegenerator to deliver energy to the plurality of electrodes, and theprogramming includes the ability to direct delivery of energy to asubset of the electrodes. The electrodes of the pattern are configuredsuch that, when receiving energy from the generator and in therapeuticcontact with a tissue target area, they ablate a portion of tissue inthe target area and leave a portion of tissue in the target areanon-ablated. In some embodiments, the electrode pattern forms a fullycircumferential surface orthogonal to its longitudinal axis, the patternsized for contacting tissue in a target area within the gastrointestinaltract. In other embodiments, the electrode pattern forms a partiallycircumferential surface orthogonal to its longitudinal axis, the patternsized for contacting tissue in a target area within the gastrointestinaltract. The partially-circumferential surface may have any arc of lessthan 360, but particular embodiments form an arc of about 180 degrees,and some particular embodiments form an arc of about 90 degrees.

In some embodiments of the system, the ablational energy elements, suchas electrodes, are distributed into a pattern such that when theprogramming directs the generator to deliver energy to all theablational energy elements, the pattern of energy-transmitting elements,when therapeutically contacted to a target tissue area, ablates aportion of tissue within the target area and does not ablate anotherportion of tissue within the target area. These embodiments typicallyhave electrodes distributed in a relatively dispersed or low-densitypattern, as it is the spacing between the electrodes that determines theconveyance or non-conveyance of energy between the electrodes. In otherembodiments, the programming directs the generator to deliver energy toa subset of electrode elements that form a pattern which, whentherapeutically contacted to a target tissue area, ablates a portion oftissue within the target area and does not ablate another portion oftissue within the target area. These embodiments typically haveelectrodes distributed in a relatively dense pattern, and the partialactivation of a subset or subsets of the dense pattern then approximatesor is functionally analogous to the less dense physical pattern, asabove, wherein the programming directs delivery of energy to allelectrodes.

The portion of the tissue that is ablated by the electrode pattern,whether by the full set of electrodes, or by a subset of electrodes, isrendered at least partially dysfunctional, and that portion of thetissue which is not ablated retains its functionality. In embodimentswhere nutrient-absorbing epithelial cells are included in the targetarea, the nutrient-absorbing cells that are ablated are compromised intheir ability to absorb nutrients, and the nutrient-absorbing cells thatare not ablated retain their nutrient-absorbing functionality. Inembodiments where endocrine cells are included in the target area, theendocrine cells that are ablated are compromised in their ability tosecrete hormones, and the endocrine cells that are not ablated retaintheir secrete hormone. In embodiments where nerve cells are included inthe target area, the nerve cells that are ablated are compromised intheir in synaptic functionality, and the nerve cells that are notablated retain their synaptic functionality.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1C provide views of an embodiment of an ablative device with afully circumferential operating radius in situ, in the alimentary tract.FIG. 1A shows an ablative device within the pylorus. FIG. 1B shows anablative device within the duodenum. FIG. 1C shows and ablative devicewithin the jejunum.

FIGS. 2A-2C provide views of an embodiment of an ablative device with apartially circumferential operating radius in situ, in an alimentarytract. FIG. 2A shows an ablative device within the gastric antrum. FIG.2B shows an ablative device within the pylorus. FIG. 2C shows anablative device within the duodenum. FIG. 2D shows and ablative devicewithin the jejunum.

FIG. 3 is a flow diagram depicting an overview of the method, wherein anappropriate site for ablational intervention for the treatment of ametabolic condition such as obesity, diabetes or metabolic syndrome isdetermined, the level of ablational therapy is determined, and at leastpreliminary information is gained regarding localization, and clinicaljudgment is exercised as to which embodiment of the invention ispreferable.

FIG. 4 is a flow diagram depicting the method after the site of ablationof a portion of the gastrointestinal tract has been localized and achoice has been made regarding the preferred ablational device. Themethod includes an evaluation of the site, including particulars oflocation, stage, determination of the number of sites, and thedimensions. The method continues with insertion of the instrument andits movement to the locale of the ablational target tissue, the morerefined movement of the ablational structure that create atherapeutically effective contact, the emission of ablational radiationand then post-treatment evaluation.

FIG. 5 is a view of an embodiment of an ablative device with a fullycircumferential operating radius.

FIG. 6 is a view of an embodiment of an ablative device with a fullycircumferential operating radius, with a balloon member in an expandedconfiguration.

FIGS. 7A-7C show the electrode patterns of the device of FIG. 5.

FIGS. 8A-8D show electrode patterns that may be used with embodiments ofthe ablative device with a fully circumferential operating radius.

FIG. 9 is a view of the ablation device of the invention with apartially circumferential operating radius.

FIG. 10 is an end view of the ablation device of the invention.

FIG. 11 is an end view of the device in an expanded configuration.

FIGS. 12, 13, and 14 are end views of the device in alternative expandedconfigurations.

FIG. 15 is a view of the ablation device of the invention in anunexpanded configuration.

FIG. 16 is a view of the ablation device of the invention in an expandedconfiguration.

FIGS. 17 and 18 are end views of the device in an expandedconfiguration.

FIG. 19A is a view of the ablation device of the invention showing adeflection member feature.

FIG. 19B is a view of the ablation device of the invention showing analternative deflection member wherein the device is in an expandedconfiguration.

FIG. 20 is a view of device shown in FIG. 19 wherein the deflectionmember is in an unexpanded configuration.

FIG. 21 is an end view of the device in an unexpanded configuration.

FIG. 22 is an end view of the device shown in FIG. 21 in an expandedconfiguration.

FIG. 23 is a view of the ablation device of the invention showing anablation structure feature.

FIG. 24 is an illustration of the ablation device of the inventioncombined with an endoscope system.

FIG. 25 is a schematic of view of a section through the wall of arepresentative organ of the gastrointestinal tract, including suchorgans as the stomach, pylorus, duodenum, and jejunum.

FIG. 26 is a view of the ablation device of the invention including anelongated sheath feature.

FIG. 27 is a view of the device wherein an elongated sheath feature isoptically transmissive.

FIG. 28 is an enlarged view of the optically transmissive feature of thedevice.

FIG. 29 is a cross sectional view of the optically transmissive sheathfeature of the device shown in FIGS. 27 and 28.

FIG. 30 is a view of the device including an alternative opticallytransmissive sheath feature and an inflation member feature in anexpanded configuration.

FIG. 31 is an illustration of the ablation device of FIG. 30 positionedwithin an esophagus.

FIG. 32 is a view of the ablation device of the invention including aslit sheath feature.

FIG. 33A is an end view of a slit sheath feature of the device whereinthe sheath is in an unexpanded configuration.

FIG. 33B is an end view of a slit sheath feature of the device and anendoscope wherein the sheath is in an expanded configuration.

FIG. 34A is a cross sectional view of the device positioned within anendoscope internal working channel wherein an inflatable member featureis in an unexpanded position.

FIG. 34B is a view of the device shown in FIG. 34A wherein theinflatable member feature is in an expanded position.

FIG. 35A is a cross sectional view of the device positioned within anendoscope internal working channel wherein an expandable member featureis in an unexpanded position.

FIG. 35B is a view of the device shown in FIG. 35A wherein theexpandable member feature is in an expanded position.

FIG. 36A is a cross sectional view of the device positioned within anendoscope internal working channel wherein an alternative expandablemember feature is in an unexpanded position.

FIG. 36B is a view of the device shown in FIG. 36A wherein theexpandable member feature is in an expanded position.

FIG. 37 is a view of the ablation device of the invention including analternative deflection member.

FIG. 38 is an illustration of the ablation device of the inventionincluding an alternative deflection member positioned within the lumenof an organ of the gastrointestinal tract in a non-deflected position.

FIG. 39 is an illustration of the device shown in FIG. 38 wherein thedeflection member is in a deflected position.

FIG. 40 is a cross sectional view of the ablation device of theinvention showing an internal coupling mechanism feature.

FIG. 41 is a cross sectional view of the ablation device of theinvention showing an alternative internal coupling mechanism and arolled sheath feature.

FIG. 42 is an illustration showing a cross sectional view of theablation device of the invention positioned within the lumen of an organof the gastrointestinal tract.

FIG. 43 is an illustration of the ablation device of the inventionpositioned within an esophagus showing a rotational feature.

FIG. 44 is an illustration of the ablation device of the inventionpositioned within an esophagus showing a rotational feature combinedwith an inflation member in an expanded configuration.

FIGS. 45A-45C are views of the ablation device of the invention showingalternative rotational features.

FIG. 46A is a view of an endoscope.

FIG. 46B is a view of the ablation device of the invention including acatheter feature.

FIG. 46C is a view of a sheath feature of the device.

FIG. 47 is a view of the ablation device of the invention including thefeatures shown in FIGS. 46A-46C in an assembly.

FIGS. 48A-48D show an electrode array with a striped pattern for afractional ablation and the ablation patterns on tissue that can be madefrom such a pattern.

FIGS. 49A and 49B show an electrode array with a concentric-circlepattern for a fractional ablation and the ablation patterns on tissuethat can be made from such a pattern.

FIGS. 50A and 50B show an electrode array with a checkerboard patternfor a fractional ablation and the ablation patterns on tissue that canbe made from such a pattern.

FIGS. 51A and 51B show an electrode array with a checkerboard patternoperating in a non-fractional manner and the ablation pattern on tissuethat is made from such an operating pattern.

FIGS. 52A and 52B show an electrode array with a checkerboard patternoperating in a fractional manner and the ablation pattern on tissue thatis made from such an operating pattern.

FIGS. 53A and 53B show an electrode array with a striped pattern ofalternating positive and negative electrodes operating in anon-fractional manner and the ablation patterns on tissue that can bemade from such an operating pattern.

FIGS. 54A and 54B show an electrode array with a striped pattern ofalternating positive and negative electrodes operating in a fractionalmanner and the ablation patterns on tissue that can be made from such anoperating pattern.

FIG. 55 shows a schematic rendering of a three dimensional view of atarget region of a radial portion of a gastrointestinal wall after ithas been ablationally treated.

DETAILED DESCRIPTION OF THE INVENTION Ablation in the GastrointestinalTract as Treatment for Metabolic Disease

Metabolic conditions such as obesity, diabetes mellitus type 2, andmetabolic syndrome tissue can be treated with an ablative techniqueapplied to portions of the wall of the gastrointestinal tract that has acontrolled depth of ablation and does not injure the deeper layers ofthe organ. Ablation technology represents a therapeutic alternative thathas been shown to be simple, safe, and effective in treating diseasesconfined to the epithelial tissue such as Barrett's esophagus andsquamous dysplasia of the esophagus, and such therapy thus holds promiseas an epithelial layer-based treatment (and in some embodiments, adeeper layer treatment) for metabolic conditions as well. The inventorshave made the inventive realization that the success of bariatricsurgery, such as Roux-en-Y gastric by-pass operations may provide arational basis for an ablational approach to an anti-obesity oranti-diabetic therapy. Although not bound by theory, for purpose ofunderstanding the invention, the hypothesis is provided that at leastsome of the effectiveness that bariatric by-pass surgery has shown isdue to a decrease or elimination of hormonal or neural signal(s) thatnormally would emanate from the stomach, pylorus, duodenum, or jejunumupon exposure to nutrient passage through the gastrointestinal tract. Byanalogy, therefore, a functional compromise as a result of awell-controlled ablation of one or more of the same organs, even in thepresence of nutrient passage, could result in a similar absence ofhormonal or neural signals, and by such same absence, obesity, diabetes,and/or metabolic syndrome may be ameliorated or cured.

Determination of an appropriate site for ablational treatment, as wellas the amount of ablational energy to be applied during such treatment,follows from the total amount of clinical information that a cliniciancan gather on a particular patient. Appropriate information to beevaluated may include, for example, the age of the patient, laboratorydata on levels of metabolic hormones such as, merely by way of example,any of insulin, glucagon, glucagon-like peptides, insulin-like growthfactors, and ghrelin, as well as data on blood glucose levels andglucose tolerance tests. In some embodiments, a preliminary endoscopicexamination of the alimentary canal may be appropriate so that anypatient-specific features may be mapped out, as well as an evaluation ofthe general dimensions of the patient's alimentary canal. Suchinformation may be obtained by direct visual observation by endoscopicapproaches with optional use of mucosal in-situ staining agents, and mayfurther be accomplished by other diagnostic methods, includingnon-invasive penetrative imaging approaches such as narrow band imagingfrom an endoscope. In one aspect, evaluation of a site includesidentifying the locale of the site, including its dimensions. In anotheraspect, evaluation of target tissue includes identifying a multiplicityof sites, if there is more than one site, and further identifying theirlocale and their respective dimensions. In still another aspect,evaluating target sites may include identifying or grading any pathologywithin the gastrointestinal tract, particularly any area overlapping ornear the areas to be targeted for ablation.

Once target sites for ablation have been identified, target tissue maybe treated with embodiments of an inventive ablational device andassociated methods as described herein. Evaluation of the status oftarget tissue sites for ablation, particularly by visualizationapproaches, may also be advantageously implemented as part of anablational therapy, as for example, in close concert with the ablation,either immediately before the application of ablational energy (such asradiant energy), and/or immediately thereafter. Further, the treatmentsite can be evaluated by any diagnostic or visual method at someclinically appropriate time after the ablation treatment, as for examplea few days, several weeks, or several few months, or at anytime whenclinically indicated following ablational therapy. Any follow-upevaluation that shows either that the therapy was unsatisfactorilycomplete, or that there is a recovery in the population of cellstargeted for ablation, a repetition of the ablational therapy may beindicated.

As described in detail herein, ablational devices have an ablationalstructure arrayed with energy-transmitting elements such as electrodes.In some embodiments, depending on the type of ablatative energy beingused in the therapy, the devices may be mounted on, or supported by anyappropriate instrument that allows movement of the ablational surface tothe local of a target site. Such instruments are adapted in form anddimension to be appropriate for reaching the target tissue site, and mayinclude simple catheters adapted for the purpose; some embodiments ofthe insertive instrument include endoscopes which in addition to theirsupportive role, also provide a visualization capability. In someembodiments of the method, an endoscope separate from the supportiveinstrument may participate in the ablational procedure by providingvisual information.

Exemplary embodiments of the inventive device as described hereintypically make use of electrodes to transmit radiofrequency energy, butthis form of energy transmission is non-limiting, as other forms ofenergy, and other forms of energy-transmission hardware are included asembodiments of the invention. Ablational energy, as provided byembodiments of the invention, may include, by way of example, microwaveenergy emanating from an antenna, light energy emanating from photonicelements, thermal energy transmitted conductively from heated ablationalstructure surfaces or as conveyed directly to tissue by heated gas orliquid, or a heat-sink draw of energy, as provided by cryonic cooling ofablational structure surfaces, or as applied by direct cold gas or fluidcontact with tissue.

Embodiments of the ablational device include variations, two of whichwill be elaborated on below, with regard to the circumferential expanseof the ablational surface to be treated. These and other variation mayprovide particular advantages depending on the nature, extent, locale,and dimensions of the one or more targeted tissue sites on the wall thealimentary canal. One embodiment of the invention includes a device withan ablational surface that is fully circumferential, i.e., encompassinga radius of 360 degrees, such that a full radial zone within a luminalorgan is subject to ablation. Within that zone, ablation may beimplemented to a varying degree, depending on the energy output and thepattern of the ablational elements (such as electrodes), but withsubstantial uniformity within the zone of ablation. This embodiment maybe particularly appropriate for treating widespread or diffuse siteswithin the gastrointestinal tract organ. In another embodiment of thedevice, the ablational surface of the inventive device is partiallycircumferential, such that it engages a fraction of the full internalperimeter or circumference of a luminal organ. The fractional portion ofthe circumference ablated on the inner surface of a luminal organdepends on the size of the luminal organ being treated (radius,diameter, or circumference) and on the dimensions of the ablationalsurface, as detailed further below. With regard to treating target sitesthat are small and discrete, the smaller or more discrete ablationalsurface provided by this latter embodiment may be advantageous.

This type of operation of a circumferential subset of ablation energyelements around a circumferential distribution of elements through 360degrees is related to the fractional operation of an electrode array, asdescribed below in the section titled “Electrode patterns and control ofablation patterns across the surface area of tissue”, where subsets ofan array of ablational elements within a relative dense pattern areactivated.

Ablation of gastrointestinal tract wall cells may be performed bydevices with ablational surface areas that vary in terms of the radialfraction of a luminal surface they ablate in a single transmission ofenergy, and absolute terms of dimension. Some embodiments of theinvention, as mentioned above described in detail below, provide a fullyradial surface, with electrodes circumferentially arrayed, thatsubstantially meets the inner surface of a luminal organ, and ablatesthrough that full range of 360 degrees. In FIGS. 1A-1C and 2A-2D, anablation device of one of two types, 100A (with an ablational surface of360 degrees) or 100B (with an ablational surface of less than 360degrees, such as the approximate 90 degree embodiment shown) issupported on an ablation catheter 41. The ablation device (100A or 100B)includes an ablation structure 101. In an embodiment where the ablationis RF-based, the ablation device typically includes an array ofelectrodes depicted in further detail in other figures, and an inflationmember or balloon 105.

FIGS. 1A-1C provide views of an embodiment of an ablative device with afully circumferential operating region in situ, in the alimentary tract.The ablative device is supported on the distal end of an elongated shaft41 of an instrument, has been inserted into the alimentary tract by anoral or nasal entry route, and has been moved into the proximity of anarea targeted for treatment. FIG. 1A shows an ablative device havingentered the gastrointestinal tract orally, having entered the stomach 7through the esophagus 6, and now within the pylorus 9. FIG. 1B shows anablative device within the duodenum 10. FIG. 1C shows and ablativedevice within the jejunum 11. Some of these embodiments with electrodesarrayed on an 360 degree ablational surface have the ability toselectively activate electrodes, such that energy is delivered across anarc of 360 degrees of the ablational surface, as for example, about 180degrees, about 90 degrees, about 45 degrees, about 30 degrees, about 10degrees, or about 5 degrees. Embodiments of these devices also vary inlength, along a longitudinal axis. By appropriate sizing in terms ofwidth (or arc) and length along the longitudinal axis, the ablationalsurface may be sized appropriately for target areas within thegastrointestinal tract.

Other embodiments of the invention provide an ablative surface with anelectrode array that addresses a fractional aspect of the inner radiusof a luminal organ in any single transmission of energy. Theseembodiments, as mentioned above, will be described in further detailbelow, in a section that follows after the description of the 360-degreecircumferential embodiment. The ablative device is supported on thedistal end of an elongated shaft 41 of an instrument, has been insertedinto the alimentary tract by the oral route, and has been moved into theproximity of an area targeted for treatment. FIG. 2A-2C provide views ofan embodiment of an ablative device with a partially circumferentialoperating radius in situ, in an alimentary tract. FIG. 2A shows anablative device within the gastric antrum 8. FIG. 2B shows an ablativedevice within the pylorus 9. FIG. 2C shows an ablative device within theduodenum 10. FIG. 2D shows and ablative device within the jejunum 11.The radial portion of a lumen that can be ablationally treated in anysingle transmission of radiant energy depends on the width of theelectrode-covered ablational surface of the embodiment of the device,and the width or diameter of the luminal organ where the treatment siteis located. The width of embodiments of the ablational surface, inabsolute terms, is described in detail below. The arc of a curvedtreatment area can be anything less than 360 degrees, however it istypically less than 180 degrees, and more particularly may include asmaller radial expanse such as a arcs of about 5 degrees, about 10degrees, about 15 degrees, about 30 degrees, about 45 degrees, about 60degrees, and about 90 degrees.

FIGS. 3 and 4 together provide flow diagram depictions of embodiments ofthe method for ablating tissue in the wall of the alimentary canal orgastrointestinal tract. The diagrams represent common aspects of theembodiments of the method, as delivered by two embodiments of thedevice, one which has a 360 degree circumferential ablation structure,and one which has an ablation structure comprising an arc of less than360 degrees.

FIG. 3 is a flow diagram depicting an overview of the method with afocus on patient evaluation and determination of a clinicallyappropriate site within the alimentary canal for ablational treatment.In another step, a responsible clinician makes an informed choice withregard to the appropriate embodiment with which to treat the patient,i.e., either the device with the 360 electrode array 100A, or the device100B with the electrodes arrayed in an arc of less than 360 degrees. Inthe event that the device 100A is chosen for use, another treatmentchoice may be made between operating the electrodes throughout the 360degree circumference, or whether to operate a radial subset of theelectrode array. In another step, a clinician further considers andmakes a determination as to the protocol for ablation, considering theamount of energy to be delivered, the energy density, the duration oftime over which energy is to be delivered. These considerations takeinto the account the surface area to be ablated, the depth of tissuewhich is to be treated, and the features of the electrode array,whether, for example, it is to be a fractional electrode, and whichpattern may be desirable. Regardless of the device chosen, anotherpreliminary step to operating the method may include a closer evaluationof the target tissue site(s) within the alimentary canal. Evaluation ofthe site may include the performance of any visualization or diagnosticmethod that provides a detailed census of the number of discrete targettissue sites, their dimensions, their precise locations, and/or theirclinical status, whether apparently normal or abnormal. This step isshown following the choice of instrument, but may occur simply inconjunction with diagnosis, or at any point after diagnosis and generallocalization of the target tissue. In any case, an evaluating step istypically performed prior to ablation, as outlined in the operationalsteps of the method, as shown in the flow diagram of FIG. 4.

FIG. 4 is a flow diagram depicting the method after the target sitewithin the gastrointestinal tract has been localized and a choice hasbeen made regarding the preferred ablational device. The method includesan evaluation of the site, including particulars of location, stage,determination of the number of sites, and the dimensions, as describedabove, and using approaches detailed in the references provided in thebackground, and/or by using whatever further approaches may be known bythose practiced in the art. The method continues with insertion of theinstrument and the movement of the ablational structure to the locale ofthe target tissue to be ablated. Subsequently, more refined movements ofthe ablational structure may be performed that create a therapeuticallyeffective contact between the ablational structure and the target tissuesite. In the event that the 360 degree embodiment of the device 100A ischosen, therapeutically effective contact may be made by inflating aballoon underlying the electrode array. In the event that the embodimentchosen is 100B, the device with an electrode surface spanning an arc ofless than 360 degrees, movements that bring the ablational surface intotherapeutically effective contact may include any of inflation of aballoon, inflation of a deflection member, and/or movement of adeflection member, all of which are described further below.

After therapeutically-effective contact is made, by either deviceembodiment 100A or 100B, and by whatever type of movement was that wastaken, a subsequent step includes the emission of ablational energy fromthe device. Variations of ablational energy emission may includeablating a single site as well as moving the instrument to a second orto subsequent sites that were identified during the evaluation step.Following the ablational event, a subsequent step may include anevaluation of the treated target site; alternatively evaluation of theconsequences of ablation may include the gathering of clinical data andobservation of the patient. In the event that an endoscope is includedin the procedure, either as the instrument supporting the ablationalstructure, or as a separate instrument, such evaluation may occurimmediately or very soon after ablation, during the procedure, wheninstruments are already in place. In other embodiments of the invention,the treated site may be evaluated at any clinically appropriate timeafter the procedure, as for example the following day, or the followingweek, or many months thereafter. In the event that any of theseevaluations show an ablation that was only partially complete, or showan undesired repopulation of targeted cells, the method appropriatelyincludes a repetition of the steps just described and schematicallydepicted in FIG. 4.

In addition to observation by direct visual approaches, or otherdiagnostic approaches of site of ablation per se, evaluation of theconsequences of ablation may include the gathering of a completespectrum of clinical and metabolic data from the patient. Suchinformation includes any test that delivers information relevant to themetabolic status of the patient such as the information gathered whendetermining the appropriateness of ablational intervention, as was madein the first step of FIG. 3.

Some embodiments of the inventive method include ablation interventionsthat are intended to be mild or partial in nature, and therebytransient. The wall of the gastrointestinal tract is a robust anddynamic biological surface, the cells of the gut are typically fastgrowing and capable of growing and repopulating areas that arecompromised. Embodiments of ablational therapeutic methods as describedherein are new and may be expected to be tailored to the particulars ofthe patient. Thus, some embodiments of the method include treatmentsthat are intended to be transient with transient effects. The transientperiod, per embodiments of the invention represent a time period duringwhich the metabolic effects of the therapy may be evaluated bydiagnostic testing and clinical observations. Based on such observationsand clinical data, the ablation may be discontinued (if results arepoor, or not-beneficial), or repeated if the results are beneficial.Repeated therapies may be tailored to be more durable. Further, based onresults, the ablation parameters may be adjusted, per clinical judgmentmade by the medical practitioner, or held constant, or ablation may beperformed at other sites.

Evaluating the Success of Ablational Treatment for Obesity, MetabolicSyndrome, or Diabetes

Restoring the metabolic condition of the patient with apathophysiological metabolic condition such as obesity, metabolicsyndrome, or diabetes toward normal may include any one or more ofdecreasing absorption of nutrients, decreasing blood glucose levels,decreasing blood insulin levels, decreasing insulin resistance,decreasing body weight, or decreasing body mass index.

Obese patients have a body mass index (BMI) of 30 kg/m2 or more. Astatistically significant and reproducible reduction in BMI compared tolevels prior to treatment per embodiments of this invention of anymagnitude would be considered an indication of therapeutic benefit.Generally, non-obese patients have a BMI that is less than 30 kg/m2.

Fasting blood glucose levels of diabetic patients are typically greaterthan 125 mg/dL. A statistically significant and reproducible reductionin fasting glucose compared to levels prior to treatment per embodimentsof this invention to of any magnitude would be considered an indicationof therapeutic benefit. Non-diabetic patients typically have fastingglucose levels of less than 125 mg/dL, for example ranging from about 70mg/dL to 110 mg/dL.

When patients undergo an oral glucose tolerance test, they drink astandard amount of a glucose solution and their blood is typically drawnfive times over a period of 3 hours. Diabetic patients typically have ablood glucose level in the range of 180 mg/dL or higher. Patients withan impaired glucose tolerance have a blood glucose level greater than140 mg/dL. A normal, non-diabetic patient has a blood glucose level lessthan or equal to 110 mg/dL. A reproducible reduction in the bloodglucose level at 2 hours following an oral glucose test compared tolevels prior to treatment per embodiments of this invention of anymagnitude would be considered an indication of therapeutic benefit.

Hemoglobin A1C (glycosylated hemoglobin) levels are used as an approachto evaluating blood glucose levels integrated over time. Diabeticpatients typically have hemoglobin A1C values 7% and higher, for exampleup 11% or 12%. Normal patients have values less than about 6%. Anyreduction in hemoglobin A1C values after treatment that arestatistically significant and reproducible would be considered anindication of therapeutic benefit.

High levels of serum insulin and the pathophysiological condition ofinsulin resistance are closely linked and occur in a state known asmetabolic syndrome as well in diabetes. Insulin levels of greater than60 pmol/L are generally considered evidence of insulin resistance. Anyreduction in serum insulin levels that are significant and repeatablecompared to insulin levels prior to treatment per embodiments of thisinvention would be considered an indication of therapeutic benefit. Thegold standard for measuring insulin resistance is performed by a methodknown as the “hyperinsulinemic euglycemic clamp”. This method isgenerally used in research studies, and not typically performed forroutine clinical diagnostic purposes. Other methods such as the“modified insulin suppression test”, the “homeostatic model assessment”(HOMA) and the “Quantitative Insulin Sensitivity Check Index” (QUICKI)are more commonly employed. All of these methods test the efficacy ofinsulin in reducing the level of glucose that has been infused into thepatient. Any reduction in the level of insulin resistance, as measuredthese methods or similar methods, that is significant and reproduciblein a patient after ablational therapy as provided by embodiments of theinvention may be considered an indication of therapeutic benefit.

Device and Method for 360 Degree Circumferential Ablation

Methods for accomplishing ablation of targeted cells within thegastrointestinal tract according to this invention include the emissionof radiant energy at conventional levels to accomplish ablation ofepithelial and with or without deeper levels of tissue injury, moreparticularly to remove or functionally compromise cells that areinvolved in the sensation of satiety or the regulation of metabolichormones such as insulin. In one embodiment, as shown in FIGS. 1A-1C, anelongated flexible shaft 41 is provided for insertion into the body inany of various ways selected by a medical care provider. The shaft maybe placed endoscopically, e.g. passing through the mouth and esophagusand then further into the gastrointestinal tract, or it may be placedsurgically, or by any other suitable approach. In this embodiment,radiant energy distribution elements or electrodes on an ablationstructure 101 are provided at a distal end of the flexible shaft 41 toprovide appropriate energy for ablation as desired. In typicalembodiments described in this section, the radiant energy distributionelements are configured circumferentially around 360 degrees.Alternatively to using emission of RF energy from the ablationstructure, alternative energy sources can be used with the ablationstructure to achieve tissue ablation and may not require electrodes.Such energy sources include: ultraviolet light, microwave energy,ultrasound energy, thermal energy transmitted from a heated fluidmedium, thermal energy transmitted from heated element(s), heated gassuch as steam heating the ablation structure or directly heating thetissue through steam-tissue contact, light energy either collimated ornon-collimated, cryogenic energy transmitted by cooled fluid or gas inor about the ablation structure or directly cooling the tissue throughcryo fluid/gas-tissue contact. Embodiments of the system and method thatmake use of these aforementioned forms of ablational energy includemodifications such that structures, control systems, power supplysystems, and all other ancillary supportive systems and methods areappropriate for the type of ablational energy being delivered.

In one embodiment the flexible shaft comprises a coaxial cablesurrounded by an electrical insulation layer and comprises a radiantenergy distribution elements located at its distal end. In one form ofthe invention, a positioning and distending device around the distal endof the instrument is of sufficient size to contact and expand the wallsof the gastrointestinal tract lumen or organ in which it is placed (e.g.the gastric antrum, the pylorus, the duodenum, or jejunum) both in thefront of the energy distribution elements as well as on the sides of theenergy distribution elements. For example, the distal head of theinstrument can be supported at a controlled distance from the wall ofthe gastrointestinal tract lumen or organ by an expandable balloon orinflation member 105A, such that a therapeutically-effective contact ismade between the ablation structure and the target site so as to allowregulation and control the amount of energy transferred to the targettissue within the lumen when energy is applied through the electrodes.The balloon is preferably bonded to a portion of the flexible shaft at apoint spaced from the distal head elements.

Another embodiment comprises using the distending or expandable balloonmember as the vehicle to deliver the ablation energy. One feature ofthis embodiment includes means by which the energy is transferred fromthe distal head portion of the invention to the membrane comprising theballoon member. For example, one type of energy distribution that may beappropriate and is incorporated herein in its entirety is shown in U.S.Pat. No. 5,713,942, in which an expandable balloon is connected to apower source that provides radio frequency power having the desiredcharacteristics to selectively heat the target tissue to a desiredtemperature. The balloon 105 of the current invention may be constructedof an electroconductive elastomer such as a mixture of polymer,elastomer, and electroconductive particles, or it may comprise anonextensable bladder having a shape and a size in its fully expandedform which will extend in an appropriate way to the tissue to becontacted. In another embodiment, an electroconductive member may beformed from an electroconductive elastomer wherein an electroconductivematerial such as copper is deposited onto a surface and an electrodepattern is etched into the material and then the electroconductivemember is attached to the outer surface of the balloon member. In oneembodiment, the electroconductive member, e.g. the balloon member 105,has a configuration expandable in the shape to conform to the dimensionsof the expanded (not collapsed) inner lumen of the human lowergastrointestinal tract. In addition, such electroconductive member mayconsist of a plurality of electrode segments arrayed on an ablationstructure 101 having one or more thermistor elements associated witheach electrode segment by which the temperature from each of a pluralityof segments is monitored and controlled by feedback arrangement. Inanother embodiment, it is possible that the electroconductive member mayhave means for permitting transmission of microwave energy to theablation site. In yet another embodiment, the distending or expandableballoon member may have means for carrying or transmitting a heatablefluid within one or more portions of the member so that the thermalenergy of the heatable fluid may be used as the ablation energy source.

A preferred device, such as that shown in FIGS. 1A-1C, includessteerable and directional control means, a probe sensor for accuratelysensing depth of cautery, and appropriate alternate embodiments so thatin the event of a desire not to place the electroconductive elementswithin the membrane forming the expandable balloon member it is stillpossible to utilize the balloon member for placement and locationcontrol while maintaining the energy discharge means at a locationwithin the volume of the expanded balloon member, such as at a distalenergy distribution head of conventional design.

In one embodiment, the system disclosed herein may be utilized as aprocedural method of treating metabolic diseases or conditions such asobesity, diabetes mellitus type 2, or metabolic syndrome. This methodincludes determination of the appropriate target sites for ablationwithin the gastrointestinal tract in order to ameliorate or eliminatesymptoms of metabolic disease, as well as the appropriate treatmentdevice, and the parameters of the ablational energy to be distributed atthe target site. After determining that the portion or portions of thegastrointestinal tract wall having this tissue that is targeted eitherfor full or partial ablation, the patient is prepared for a procedure ina manner appropriate according to the embodiment of the device to beutilized. Then, the practitioner inserts, in one embodiment, viaendoscopic access and control, the ablation device shown and discussedherein through the mouth of the patient. Further positioning of portionsof the device occurs as proper location and visualization identifies theablation site in the gastrointestinal tract. Selection and activation ofthe appropriate quadrant(s) or portion(s)/segment(s) on the ablationcatheter member is performed by the physician, including appropriatepower settings according to the depth of cautery desired. Additionalsettings may be necessary as further ablation is required at differentlocations and/or at different depths within the patient'sgastrointestinal tract. Following the ablation, appropriate follow-upprocedures as are known in the field are accomplished with the patientduring and after removal of the device from the gastrointestinal tract.The ablation treatment with ultraviolet light may also be accompanied byimproved sensitizer agents, such as hematoporphyrin derivatives such asPhotofrine™ porfimer sodium, registered trademark of Johnson & JohnsonCorporation, New Brunswick, N.J.

In yet another method of the invention, the practitioner may firstdetermine the length of the portion of the gastrointestinal tractrequiring ablation and then may choose an ablation catheter from aplurality of ablation catheters of the invention, each catheter having adifferent length of the electrode member associated with the balloonmember. For example, if the practitioner determines that 1 centimeter ofthe gastrointestinal tract surface required ablation, an ablationcatheter having 1 centimeter of the electrode member can be chosen foruse in the ablation. The length of the electrode member associated withthe balloon member can vary in length from 1 to 10 cm.

In yet another embodiment, a plurality of ablation catheters wherein theradiant energy distribution elements are associated with the balloonmember can be provided wherein the diameter of the balloon member whenexpanded varies from 12 mm to 40 mm. In this method, the practitionerwill choose an ablation catheter having a diameter when expanded whichwill cause the gastrointestinal tract to stretch and the mucosal layerto thin out, thus, reducing or occluding blood flow at the site of theablation. It is believed that by reducing the blood flow in the area ofablation, the heat generated by the radiant energy is less easilydispersed to other areas of the target tissue thus focusing the energyto the ablation site.

One approach a practitioner may use to determine the appropriatediameter ablation catheter to use with a particular patient is to use ina first step a highly compliant balloon connected to a pressure sensingmechanism. The balloon may be inserted into a luminal organ within thegastrointestinal tract and positioned at the desired site of theablation and inflated until an appropriate pressure reading is obtained.The diameter of the inflated balloon may be determined and an ablationdevice of the invention having a balloon member capable of expanding tothat diameter chosen for use in the treatment. In the method of thisinvention, it is desirable to expand the expandable electroconductivemember such as a balloon sufficiently to occlude the vasculature of thesubmucosa, including the arterial, capillary or venular vessels. Thepressure to be exerted to do so should therefore be greater than thepressure exerted by such vessels.

Electrode Patterns and Control of Ablation Patterns Across the SurfaceArea of Tissue

Some aspects of embodiments of the ablational device and methods of usewill now be described with particular attention to the electrodepatterns present on the ablation structure. The device used is shownschematically in FIGS. 5-7. As shown in FIG. 6, the elongated flexibleshaft 41 is connected to a multi-pin electrical connector 94 which isconnected to the power source and includes a male luer connector 96 forattachment to a fluid source useful in expanding the expandable member.The elongated flexible shaft has an electrode 98 wrapped around thecircumference. The expandable member of the device shown in FIGS. 5 and6 further includes three different electrode patterns, the patterns ofwhich are represented in greater detail in FIGS. 7A-7C. Typically, onlyone electrode pattern is used in a device of this invention, althoughmore than one may be included. In this particular device, the elongatedflexible shaft 41 comprises six bipolar rings 62 with about 2 mmseparation at one end of the shaft (one electrode pattern), adjacent tothe bipolar rings is a section of six monopolar bands or rectangles 65with about 1 mm separation (a second electrode pattern), and anotherpattern of bipolar axial interlaced finger electrodes 68 is positionedat the other end of the shaft (a third electrode pattern). In thisdevice, a null space 70 is positioned between the last of the monopolarbands and the bipolar axial electrodes. The catheter used in the studywas prepared using a polyimide flat sheet of about 1 mil (0.001″)thickness coated with copper. The desired electrode patterns were thenetched into the copper.

The electrode patterns of the invention may vary; other possibleelectrode patterns are shown in FIGS. 8A-8D as 80, 84, 88, and 92,respectively. Pattern 80 is a pattern of bipolar axial interlaced fingerelectrodes with about 0.3 mm separation. Pattern 84 includes monopolarbands with 0.3 mm separation. Pattern 88 is that of electrodes in apattern of undulating electrodes with about 0.25 mm separation. Pattern92 includes bipolar rings with about 0.3 mm separation. In this case theelectrodes are attached to the outside surface of an esophageal dilationballoon 72 having a diameter of about 18 mm. The device may be adaptedto use radio frequency by attaching wires 74 as shown in FIG. 5 to theelectrodes to connect them to the power source.

The preceding electrode array configurations are described in thecontext of an ablation structure with a full 360 degree ablationsurface, but such patterns or variants thereof may also be adapted forablation structures that provide energy delivery across a surface thatis less than completely circumferential, in structures, for example,that ablate over any portion of a circumference that is less than 360degrees, or for example structures that ablate around a radius of about90 degrees, or about 180 degrees.

Embodiments of the ablation system provided herein are generallycharacterized as having an electrode pattern that is substantially flaton the surface of an ablation support structure and which isnon-penetrating of the tissue that it ablates. The electrode patternforms a contiguous treatment area that comprises some substantial radialaspect of a luminal organ; this area is distinguished from ablationalpatterns left by electrical filaments, filament sprays, or single wires.In some embodiments of the invention the radial portion may be fullycircumferential; the radial portion of a luminal organ that is ablatedby embodiments of the invention is function of the combination of (1)the circumference of the organ, which can be large in the case ofstomach, and small when in the case of the pylorus or a region in thesmall intestine, and (2) the dimensions of the electrode pattern. Thus,at the high end, as noted, the radial expanse of a treatment area may beas large as 360 degrees, and as small as about 5 to 10 degrees, as couldbe the case in a treatment area within the stomach.

Embodiments of the ablational system and method provided are alsocharacterized by being non-penetrating. Ablational radiofrequency energyis delivered from the flat electrode pattern as it makes therapeuticcontact with the tissue surface of a treatment area, as describedelsewhere in this application; and from this point of surface contact,energy is directly inwardly to underlying tissue layers.

Embodiments of the ablational system and method provided herein arefurther characterized by the electrode pattern being configured suchthat only a portion of the tissue surface receives sufficientradiofrequency energy to achieve ablation and another portion of thesurfaces receives insufficient energy to achieve ablation. The systemand method are further configured to control the delivery ofradiofrequency energy inwardly from the tissue surface such that depthof tissue layers to which energy sufficient for ablation is delivered iscontrolled.

Controlling the fraction of the tissue surface target area that isablated comes about by having some fraction of the tissue ablated, atleast to some degree, and having some fraction of the surface within thetarget area emerge from the treatment substantially free of ablation.The ability to control the ratio of ablated and non-ablated surfaceprovides substantial benefit to the treatment. The ablational targetareas in this method, after all, are not cancerous, in which case theircomplete ablation may be desired, and in fact the target areas may notbe abnormal in any sense. The ablational treatment, per embodiments ofthis invention, is directed not necessarily toward correcting any defectof the target tissue, but rather toward a larger therapeutic end, where,in fact, that end is served by creation of a modulated dampening of thenormal function of the target area. It is not likely, for example, whentreating a metabolic condition such as obesity or diabetes, that it isdesirable to render a complete ablation, it is far more likely that whatis desired is a modulated approach, where a varying degree ofdysfunction can be provided, without substantially damaging the organ,or a particular layer of the organ. Stated in another way, it isgenerally desirable for the health of the organ within which the targetarea is located, and for the health of the individual as a whole, thatsome degree of normal functioning remain after ablation.

By way of an illustrative example as to what is desirable and beingprovided by the invention, the organ in which the ablation target areais located can be appreciated as a population of particular target cellswithin the tissue of the target area, which can function, based on theirhealth, at a functional capacity at some low threshold of 20%, forexample, when in poor condition, and at 100%, when in optimal condition.The object of the ablational treatment provided herein, within thisexample by analogy is not to render the full population of cells to bedysfunctional and operating at 50% capacity. The object of the inventionis to have some fraction of the cells within the population,post-ablational treatment, to remain fully functional, operating atabout 100% capacity, and to have some remaining fraction operating at arange of lower capacity.

Controlling the fraction of the tissue surface target area that isablated, per embodiments of the invention, is provided by variousexemplary approaches: for example, by (1) the physical configuration ofelectrode pattern spacing in a comparatively non-dense electrodepattern, and by (2) the fractional operation of a comparatively denseelectrode array, in a billboard-like manner. Generally, creating afractional ablation by physical configuration of the electrode patternincludes configuring the electrode pattern such that some of the spacingbetween electrodes is sufficiently close that the conveyance of a givenlevel of energy between the electrodes sufficient to ablate tissue isallowed, and other spacing between electrodes is not sufficiently closeenough to allow conveyance of the level of energy sufficient to ablate.Embodiments of exemplary electrode patterns that illustrate thisapproach to creating fractional ablation are described below, anddepicted in FIGS. 48-50. The creation of an ablation pattern byactivating a subset of electrodes represents an operation of theinventive system and method which is similar to the described above,wherein an ablational structure with a fully circumferential pattern ofelectrodes can be operated in a manner such that only a radial fractionof the electrodes are operated.

The ablation system of the invention includes an electrode pattern witha plurality of electrodes and a longitudinal support member supportingthe electrode pattern, as described in numerous embodiments herein.Energy is delivered to the electrodes from a generator, and theoperation of the generator is controlled by a computer controller incommunication with the generator, the computer controller controllingthe operating parameters of the electrodes. The computer controller hasthe capability of directing the generator to deliver energy to all theelectrodes or to a subset of the electrodes. The controller further hasthe ability to control the timing of energy delivery such thatelectrodes may be activated simultaneously, or in subsets,non-simultaneously. Further, as described elsewhere, the electrodes maybe operated in a monopolar mode, in a bipolar mode, or in a multiplexingmode. These various operating approaches, particularly by way ofactivating subsets of electrodes within patterns, allow the formation ofpatterns that, when the pattern is in therapeutic contact with a targetsurface, can ablate a portion of tissue in the target area, and leave aportion of the tissue in the target area non-ablated.

Generally, creating a fractional ablation by an operational approachwith a comparatively dense electrode array includes operating theelectrode pattern such that the energy delivered between some of theelectrodes is sufficient to ablate, whereas energy sufficient to ablateis not delivered between some of the electrodes. Embodiments ofexemplary electrode patterns that illustrate this approach to creatingfractional ablation are described below, and depicted in FIGS. 51-54.

Another aspect of controlling the fraction of tissue ablation, perembodiments of the invention, relates to controlling the depth ofablation into tissue layers within the target area. Energy is deliveredinwardly from the surface, thus with modulated increases in energydelivery, the level of ablation can be controlled such that, forexample, the ablated tissue may consist only of tissue in the epitheliallayer, or it may consist of tissue in the epithelial layer and thelamina propria layers, or it may consist of tissue in the epithelial,lamina propria and muscularis mucosal layers, or it may consist oftissue in the epithelial, lamina propria, muscularis mucosa, andsubmucosal layers, or it may consist of tissue in the epithelial layer,the lamina propria, the muscularis mucosae, the submucosa, and themuscularis propria layers. In no instance is ablational energy deliveredto the serosal layer of the gastrointestinal tract.

Embodiments of the invention include RF electrode array patterns thatablate a fraction of tissue within a given single ablational area,exemplary fractional arrays are shown in FIGS. 48A, 49A, and 50A. Thesefractional ablation electrode arrays may be applied, as above, to aboveto ablational structures that address a fully circumferential targetarea, or a structure that addresses any portion of a full circumferencesuch as 90 degree radial surface, or a 180 degree radial surface. FIG.48A shows a pattern 180 of linear electrodes 60 aligned in parallel asstripes on a support surface. The electrodes are spaced apartsufficiently such that when pressed against tissue in therapeuticcontact, the burn left by distribution of energy through the electrodesresults in a striped pattern 190 on the target tissue as seen in FIG.48B corresponding to the electrode pattern, with there being stripes ofburned or ablated tissue 3 a that alternate with stripes of unburned, orsubstantially unaffected tissue 3 b. In some embodiments of the method,particularly in ablation structures that address a target area of lessthan 360 radial degrees, such as a target surface that is about 180degrees, or more particularly about 90 degrees of the innercircumference of a lumen, the ablation may be repeated with theablational structure positioned at a different angle. FIG. 48C, forexample, depicts a tissue burn pattern 191 created by a first ablationalevent followed by a second ablational event after the ablationalstructure is laterally rotated by about 90 degrees. FIG. 48D, foranother example, depicts a tissue burn pattern 192 created by a firstablational event followed by a second ablational event after theablational structure is laterally rotated by about 45 degrees.

The effect of an ability to ablate a tissue surface in this manner addsanother level of fine control over tissue ablation, beyond suchparameters as total energy distributed, and depth of tissue ablation.The level of control provided by fractional ablation, and especiallywhen coupled with repeat ablational events as described above in FIGS.48C and 48D, is to modulate the surface area-distributed fraction oftissue that is ablated to whatever degree the local maximal ablationlevel may be. The fractional ablation provided by such fractionalelectrode pattern may be particularly advantageous when the effects ofablation are not intended to be absolute or complete, but instead afunctional compromise of tissue, or of cells within the tissue isdesired. In some therapeutic examples, thus, a desirable result could bea partial reduction in overall function of a target area, rather than atotal loss of overall function. Another example where such fractionalablation may be desirable is in the case where ablation is intended tobe temporary or transient. In a fractional ablation of a target area inthe wall of a gastrointestinal lumen, for example, a desirable resultmay be the transient compromise of tissue during which time the effectof such compromise may be evaluated. In an ablation pattern thatincludes a burned area 3 a and an unburned area 3 b, it can beunderstood that cells from the unburned area could give rise to cellsthat would migrate or repopulate the denuded area within the burned area3 b.

FIGS. 49A and 50A depict other examples of a fractionally-ablatingelectrode pattern on an ablation structure, and FIGS. 49B and 50B showthe respective fractional burn patterns on tissue that have been treatedwith these electrode patterns. In FIG. 49A a pattern of concentriccircles 182 is formed by wire electrodes that (from the center andmoving outward) form a +−−++− pattern. When activated, the tissuebetween +− electrodes is burned, and the tissue between ++ electrodepairs or −− electrode pairs is not burned. Thus, the concentric pattern192 of FIG. 49B is formed. Embodiments of fractionally-ablatingelectrode patterns such as those in FIG. 49A need not include perfectcircles, and the circles (imperfect circles or ovals) need not beperfectly concentric around a common center.

Similarly, FIG. 50A shows a checkerboard pattern 184 of + and −electrodes which when activated create a burn pattern 194 as seen inFIG. 50B. Tissue that lies between adjacent + and − electrodes isburned, while tissue that lies between adjacent ++ electrodes or −−electrode pairs remains unburned. FIG. 50B includes a representation ofthe location of the + and − electrodes from the ablation structure inorder to clarify the relative positions of areas that are burned 3 a andthe areas that remain substantially unburned 3 b.

Embodiments of the invention include RF electrode array patterns thatablate a fraction of tissue within a given single ablational area byvirtue of operational approaches, whereby some electrodes of a patternare activated, and some are not, during an ablational event visited upona target area. Exemplary fractional arrays are shown in FIGS. 51A, 52A,53A and 54A. These fractional ablation electrode arrays may be applied,as above, to ablational structures that address a fully circumferentialtarget area, or a structure that addresses any portion of a fullcircumference such as, by way of example, a 90 degree radial surface, ora 180 degree radial surface.

FIG. 51A shows a checkerboard electrode pattern during an ablationalevent during which all electrode squares of the operational pattern 186Aare operating, as depicted by the sparkle lines surrounding eachelectrode. Operating the electrode pattern 186A in this manner producesan ablation pattern 196A, as seen in FIG. 51B, wherein the entiresurface of tissue within the treatment area is ablated tissue 3 a. FIG.52A, on the other hand, shows a checkerboard electrode pattern during anablational event during which only every-other electrode square of theoperational pattern 186A is operating, as depicted by the sparkle linessurrounding each activated electrode. Operating the electrode pattern186B in this manner produces an ablation pattern 196B, as seen in FIG.52B, wherein a checkerboard fractionally ablated pattern with adispersed pattern of ablated squares 3 a of tissue 3 a alternate withsquare areas of tissue 3 b that are not ablated.

FIG. 53A shows a striped linear electrode pattern of alternating + and −electrodes during an ablational event during which all electrode squaresof the operational pattern 188A are operating, as depicted by thesparkle lines surrounding each linear electrode. Operating the electrodepattern in this manner 188A produces an ablation pattern 198A, as seenin FIG. 53B, wherein the entire surface of tissue within the treatmentarea is ablated tissue 3 a.

FIG. 54A, on the other hand, shows a striped linear electrode pattern188B of alternating + and − electrodes during an ablational event duringwhich alternate pairs of the linear electrode pairs are operating, asdepicted by the sparkle lines surrounding the activated linearelectrodes. Operating the electrode pattern in this manner 188B producesan ablation pattern 198A, as seen in FIG. 54B, wherein stripes ofablated tissue 3 a within the treatment area alternate stripes ofnon-ablated tissue 3 b.

FIG. 55 is a schematic rendering of a three dimensional view of a targetregion of a radial portion of a gastrointestinal wall after it has beenablationally treated, per embodiments of the invention. Ablated regions3 a are rendered as conical regions distributed through the target areawithin a larger sea of non-ablated tissue 3 b. The conical regions 3 aare of approximately the same depth, because of the control exerted overthe depth of the ablation area, as described herein. The conical regionsare of approximately the same width or diameter, and distributed evenlythroughout the tissue, because of the control over ablational surfacearea, as described herein. In this particular example, the therapeutictarget is actually a particular type of cell 4 b (open irregularspheres), for example, a nerve cell, or endocrine secretory cell; andthese cells are distributed throughout the target area. Thepost-ablation therapeutic target cells 4 a (dark irregular spheres) arethose which happened to be included within the conical regions 3 a thatwere ablated. The post-ablation cells 4 a may be rendered dysfunctionalto varying degree, they may be completely dysfunctional, they may be,merely by way of illustrative example, on the average, 50% functional bysome measure, and there functionality may vary over a particular range.It should be particularly appreciated however, per embodiments of theinvention, that the cells 4 b, those not included in the ablated tissuecones, are fully functional.

Controlling the Ablation in Terms of the Tissue Depth of the AblationEffect

In addition to controlling the surface area distribution of ablation, asmay be accomplished by the use of fractional ablation electrodes asdescribed above, or as controlled by the surface area of electrodedimensions, ablation can be controlled with regard to the depth of theablation below the level of the tissue surface where the ablativestructure makes therapeutic contact with the tissue. The energy deliveryparameters appropriate for delivering ablation that is controlled withregard to depth in tissue may be determined experimentally. By way ofexample, an experimental set of exercises was performed on normalimmature swine in order to understand the relationship between theelectrical parameters of electrode activation and the resultant level ofablation in esophageal tissue. The data are shown in detail in U.S.application Ser. No. 10/370,645 of Ganz et al., filed on Feb. 19, 2003,and in the publication on Aug. 21, 2003, of that application, US2003/0158550 A1, particularly in Tables 1-4 of that application. By anapproach such as this, appropriate parameters for ablation of othertissues in the gastrointestinal tract may be determined. Such parametersas applied by ablational electrode patterns on an ablational structurewith a 360 degree operating surface that is directed to esophagealtissue, by way of example, include 300 W delivered within 300 msec, witha tightly spaced with tightly spaced bi-polar electrode array (less than250 microns). Ablation depth related to the energy density deliveredwith 8-12 J/cm2 results in complete removal of the epithelium. Suchparameters as applied by electrode patterns on an ablation structurewith an operating radial surface of about 90 degrees includes multiplenarrow band electrodes spaced 250 microns wide, where the generatordelivers very high power energy density at 40 W/cms to the tissue in anenergy dosage of 12-15 J/cm2. In general, depth variances can beachieved via time of ablation, dosage, number of energy applications,and electrode spacing.

FIG. 25 provides a schematic representation of the histology of thegastrointestinal wall as it is found in various luminal organs such asthe esophagus, stomach, pylorus, duodenum, and jejunum. The relativepresence and depth and composition of the layers depicted in FIG. 25vary from organ to organ, but the basic organization is similar. Thelayers of the gastrointestinal wall will be described in their orderfrom the innermost to the outermost layer facing the gastrointestinallumen; and as seen FIG. 25 and in terms of the direction from which anablational structure would approach the tissue. The innermost layer canbe referred to as the surface (epithelium), and succeeding layers can beunderstood as being below or beneath the “upper” layers. The innermostlayer of a gastrointestinal tract organ, which is in direct contact withthe nutrients and processed nutrients as they move through the gut is alayer of epithelium 12. This layer secretes mucous which protects thelumen from abrasion and against the corrosive effect of an acidicenvironment. Beneath the epithelium is a layer known as the laminapropria 13, and beneath that, a layer known as the muscularis mucosae14. The epithelium 12, the lamina propria 13, and the muscularis mucosae14 collectively constitute the mucosa 15.

Below the mucosal layer 15 is a layer known as the submucosa 16, whichforms a discrete boundary between the muscosal layer 15 above, and themuscularis propria 17 below. The muscularis propria 17 includes variousdistinct layers of smooth muscle that enwrap the organ, in variousorientations, including oblique, circular, and the longitudinal layers.Enwrapping the muscularis propria 17 is the serosa 18, which marks theouter boundary of the organ.

The entirety of the gastrointestinal tract wall is highly vascular andinnervated. The mucosal layer is particular rich in glands and cellsthat secrete contents into the lumen and secrete hormones into thebloodstream. The nerves in this region are sensitive to the chemicalcomposition of the nutrient flow, as it passes by, and their synapticsignals convey information to other organs that are involved in nutrientprocessing, such as the pancreas, and to the central nervous system,where information is integrated and regulates appetite and satiety.Nerve cells, proprioreceptors, in the muscularis propria sense thephysical state of the wall, whether it is contracted or extended, andmotor neurons in the musculature control the tension and generalmotility of the organ. All of these cells, including vasculature,exocrine cells, endocrine cell, and nerve cells are potential targetsfor ablation when ablational energy is directed toward the region inwhich they reside. As a result of receiving energy, cells may be killedor scarred to an extent that they are no longer functional, or they maybe partially damaged, leaving some level of function. Additionally, itshould be understood that these cells all exist in populations, and apartial ablation may manifest in a statistical distribution of damage,in which some cells of the population are eliminated or damaged beyondredemption, and some cells may remain substantially unaffected, andfully functional. In such partial or fractional ablation events, it canbe understood that the remnant level of function following therapeuticablation may include a range of function and dysfunction. It can also beappreciated that by such partial ablations, in some cases, damage may betransient. Recovery from transient damage may occur by any one or moreof several broad mechanisms. For example, in some cases, individualcells may be damaged by the ablational energy, but in time they canrecover their function. In other cases, cell populations can recover byregrowing or repopulating. For example, if a fraction of a population iseliminated, the local environment may encourage the division ofsurviving cells, or of resident stem cells to multiply, and have thepopulation recover to its pre-ablational state. In still otherinstances, cells may migrate into damaged areas, and contribute tofunctional recovery by their presence. Further, as a result of ablation,a receptor or cell may be covered up by new tissue involved in thehealing process rendering the receptor or cell either more or lesssensitive and responsive. Still further, the tissue around the receptoror cell may heal after ablation in a manner that renders the receptor orcell either more or less sensitive and responsive.

As provided by embodiments of the invention, the ablation applied togastrointestinal wall tissue may be depth-controlled, such that only theepithelium 12, or only a portion of the mucosal layer is ablated,leaving the deeper layers substantially unaffected. In otherembodiments, the ablated tissue may commence at the epithelium yetextend deeper into the submucosa and possibly the muscularis propria, asnecessary to achieve the desired therapeutic effect.

Device and Method for Partially-Circumferential Ablation

One embodiment of a method of ablating tissue in the gastrointestinaltract includes the use of an ablation device with an ablation structuresupported by conventional endoscopes 111, as illustrated in FIG. 24. Asdescribed herein, more particularly, the tissue targeted for ablation byembodiments of an ablation device and methods therefore is on the wallof the gastrointestinal tract in the lumen of an organ such as thestomach, pylorus, duodenum, or jejunum. An example of one commerciallyavailable conventional endoscope 111 is the Olympus “gastrovideoscope”model number GIF-Q160. While the specific construction of particularcommercially available endoscopes may vary, as shown in FIG. 24, mostendoscopes include a shaft 164 having a steerable distal end 110 and ahub or handle 162 which includes a visual channel 161 for connecting toa video screen 160 and a port 166 providing access to an inner workingchannel within the shaft 164. Dials, levers, or other mechanisms (notshown) will usually be provided on the handle 162 to allow an operatorto selectively steer the distal end 110 of the endoscope 111 as is wellknown in the endoscopic arts. In accordance with the present invention,an ablation device, including an ablation structure is advanced into thegastrointestinal tract while supported at the distal end of anendoscope. The ablation structure is deflectable toward a tissue surfaceand the ablation structure is activated to ablate the tissue surface.Within the gastrointestinal tract, variously sized tissue surface sitescan selectively be ablated using the device. As will be furtherdescribed, the ablational structure of embodiments described in thissection do not circumscribe a full 360 degrees, but rather circumscribea fraction of 360 degrees, as will be described further below.

In general, in one aspect a method of ablating tissue in thegastrointestinal tract is provided. The method includes advancing anablation structure into the gastrointestinal tract while supporting theablation structure with an endoscope. In some embodiments, advancing thestructure into the gastrointestinal may be sufficient to place theablational structure of the device into close enough proximity in orderto achieve therapeutic contact. In other embodiments, a subsequent stepmay be undertaken in order to achieve an appropriate level oftherapeutic contact. This optional step will be generally be understoodas moving the ablation structure toward the target site. The method thusmay further include moving at least part of the ablation structure withrespect to the endoscope and toward a tissue surface; and activating theablation structure to ablate the tissue surface. Moving at least part ofthe ablation structure with respect to the endoscope can include, but isnot limited to movement toward, away from or along the endoscope. Movingthe ablational structure toward a target tissue surface may be performedby structures in ways particular to the structure. For example, thestructure can be moved by inflating a balloon member, expanding adeflection member, or moving a deflection member. The function of suchmovement is to establish a therapeutically effective contact between theablational structure and the target site. A therapeutically effectivecontact includes the contact being substantial and uniform such that thehighly controlled electrical parameters of radiant emission from theelectrode result in similarly highly controlled tissue ablation. Someembodiments of the invention further include structure and method forlocking or securing such a therapeutically effective contact onceestablished. Thus, some embodiments include a position locking stepthat, for example, uses suction to secure the connection between theablation structure and the tissue site.

As shown in FIGS. 9, 10, 11, and 26, in one aspect a method of ablatingtissue in the esophagus includes an ablation device 100 for ablating atissue surface 3, wherein the device 100 includes an ablating structure,for example, an ablation structure 101 supported by an endoscope 111.The method includes ablating tissue in the wall of a luminal organ ofthe gastrointestinal tract by the steps of (1) advancing the ablationstructure 101 into the luminal organ; (2) deflecting the ablationstructure 101 toward a tissue surface 3; and (3) activating the ablationstructure to ablate the tissue surface 3. As shown in FIG. 9, the device100 can additionally include a housing 107, electrical connections 109,an inflation line 113 and an inflation member or balloon 105.

The ablation structure 101, in one embodiment is an electrode structureconfigured and arranged to deliver energy comprising radiofrequencyenergy to the mucosal layer of the wall of the organ of thegastrointestinal tract. It is envisioned that such an ablation structure101 can include a plurality of electrodes. For example, two or moreelectrodes may be part of an ablation structure. The energy may bedelivered at appropriate levels to accomplish ablation of mucosal orsubmucosal level tissue, or alternatively to cause therapeutic injury tothese tissues, while substantially preserving muscularis tissue. Theterm “ablation” as used herein generally refers to thermal damage to thetissue causing any of loss of function that is characteristic of thetissue, or tissue necrosis. Thermal damage can be achieved throughheating tissue or cooling tissue (i.e. freezing). In some embodimentsablation is designed to be a partial ablation. In other embodiments.Advantageously, in some embodiments, healing is more rapid and strictureformation in the tissues is minimized when such a completely ablationalapproach is used.

Although radiofrequency energy, as provided by embodiments of theinvention, is one particular form of energy for ablation, otherembodiments may utilize other energy forms including, for example,microwave energy, or photonic or radiant sources such as infrared orultraviolet light, the latter possibly in combination with improvedsensitizing agents. Photonic sources can include semiconductor emitters,lasers, and other such sources. Light energy may be either collimated ornon-collimated. Other embodiments of this invention may utilize heatablefluids, or, alternatively, a cooling medium, including such non-limitingexamples as liquid nitrogen, Freon™, non-CFC refrigerants, or CO₂ as anablation energy medium. For ablations using hot or cold fluids or gases,the ablation system may include an apparatus to circulate theheating/cool medium from outside the patient to the heating/coolingballoon or other element and then back outside the patient again.Mechanisms for circulating media in cryosurgical probes are well knownin the ablation arts. For example, and incorporated by reference herein,suitable circulating mechanisms are disclosed in U.S. Pat. No. 6,182,666to Dobak; U.S. Pat. No. 6,193,644 to Dobak; U.S. Pat. No. 6,237,355 toLi; and U.S. Pat. No. 6,572,610 to Kovalcheck.

In a particular embodiment, the energy delivered to the wall of aluminal organ of the gastrointestinal tract comprises radiofrequencyenergy that can be delivered from the energy delivery device 100.Radiofrequency energy can be delivered in a number of ways. Typically,the radiofrequency energy will be delivered in a bipolar fashion from abipolar array of electrodes positioned on the ablation structure 101, insome cases on an expandable structure, such as a balloon, frame, cage,or the like, which can expand and deploy the electrodes directly againstor immediately adjacent to the mucosal tissue so as to establish acontrolled level of therapeutic contact between the electrodes and thetarget tissue (e.g., through direct contact or through a dielectricmembrane or other layer). Alternatively, the electrode structure mayinclude a monopolar electrode structure energized by a radiofrequencypower supply in combination with a return electrode typically positionedon the patient's skin, for example, on the small of the back. In anycase, the radiofrequency energy is typically delivered at a high energyflux over a very short period of time in order to injure or ablate onlythe mucosal or submucosal levels of tissue without substantially heatingor otherwise damaging the muscularis tissue. In embodiments where theablation structure includes a plurality of electrodes, one or more ofthe electrodes can be bipolar or monopolar, and some embodiments includecombinations of bipolar and monopolar electrodes.

The ablation structure 101 can be arranged and configured in any of anumber ways with regard to shape and size. Typically, the array has anarea in the range from about 0.5 cm² to about 9.0 cm². Typical shapeswould include rectangular, circular or oval. In one embodiment, theablation structure 101 has an area of about 2.5 cm². In anotherembodiment, the ablation structure 101 has an area of about 4 cm² anddimensions of about 2 cm. by 2 cm.

The housing 107 of the ablation device 100 is arranged and configured tosupport the ablation structure 101. The housing 107 can be made of anysuitable material for withstanding the high energy flux produced by theablation structure 101. As shown in FIGS. 9-14, 17, 18, 21, and 22, inone embodiment, the housing 107 is sandwiched between the ablationstructure 101 and an endoscope 111 when the ablation device 100 issupported by an endoscope 111. One end of the ablation structure 101 canbe further away from the endoscope than the other end to improve ease ofcontact with the targeted tissue (not shown). For example, to ensure theproximal end of the ablation structure 101 makes contact with thetargeted tissue, the proximal end of the electrode may be supported by atapered housing member 107.

The electrical connections 109 of the ablation device connect theablation structure 101 to a power source. The electrical connections 109can include a single wire or plurality of wires as needed to providecontrolled energy delivery through the ablation structure 101. In oneembodiment, the electrical connections 109 include low electrical losswires such as litz wire.

The inflation line 113 is arranged and configured to transport anexpansion medium, typically a suitable fluid or gas, to and from theinflation member. In one embodiment, the inflation line is a flexibletube. The inflation line 113 can be made of polymer or co-polymers, suchas the non-limiting examples of polyimide, polyurethane, polyethyleneterephthalate (PET), or polyamides (nylon). The inflation member 105 isdesigned to deflect the ablation device 100 in relation to a targettissue surface 3. The inflation member 105 can be reversibly expanded toan increased profile.

In one embodiment, the inflation member 105 additionally serves as anattachment site for support of the ablation device 100 by an endoscope111. As shown in FIGS. 9-14, 17, 18, 21 and 22, the inflation member 105can be deployed from a low profile configuration or arrangement (seeFIGS. 10, and 20) to an increased profile configuration or arrangement(see FIGS. 11-14, 17-19) using the expansion medium. In preparation forablation, when the inflation member 105 is sufficiently inflated,deflection of the ablation device 100 in relation to a tissue surface 3can be achieved. As shown in FIGS. 11, 31, 42, and 44, in oneembodiment, deflection of the ablation device 100 results in atherapeutic level of contact, i.e., a substantially direct, uniform, andsustainable contact between the ablation structure 101 of the device 100and the target tissue surface 3. For example, as shown in FIGS. 31, 42,and 44, when the inflation member 105 is sufficiently inflated, theresulting expanded profile of the inflation member 105, which contactsthe tissue surface 3, results in contact by deflection between thetissue surface 3 of the inner wall of a luminal organ gastrointestinaltract 5 and the ablation structure 100. In these embodiments, suctioncan be applied in combination with the inflation member 105 to achievecontact between the ablation structure 101 and the tissue surface 3.Suction can be achieved through the endoscope 111 or through theablation device 100 to aid in collapsing the targeted tissue surface 3around the ablation structure 101.

In various embodiments, the inflation member 105 may be compliant,non-compliant or semi-compliant. The inflation member 105 can be made ofa thin, flexible, bladder made of a material such as a polymer, as byway of non-limiting examples, polyimide, polyurethane, or polyethyleneterephthalate (PET). In one embodiment, the inflation member is aballoon. Inflation of the inflation member 105 can be achieved throughthe inflation line 113 using, for example, controlled delivery of fluidor gas expansion medium. The expansion medium can include a compressiblegaseous medium such as air. The expansion medium may alternativelycomprise an incompressible fluid medium, such as water or a salinesolution.

As shown in FIGS. 12, 13, and 14, the inflation member 105 can beconfigured and arranged in a variety of ways to facilitate deflection ofthe ablation device 100 in relation to a tissue surface 3. For example,as shown in FIG. 12, the inflation member 105 can be eccentricallypositioned in relation to the supporting endoscope 111 as well as thehousing 107 and the ablation structure 101. Alternatively, as shown inFIG. 13, the inflation member 105 can be positioned concentrically inrelation to the supporting endoscope 111 and the ablation structure 101can be attached to the inflation member 105 distally from the endoscope111. In another embodiment, as shown in FIG. 12, the inflation member105 can be positioned between the supporting endoscope 111 and theablation structure 101. The ablation structure 101 shown in FIGS. 12-14can cover a range of circumferential span of the endoscope 111 spanning,for example, from about 5 to 360 degrees when inflation member 105 isdeployed.

One method of ablating tissue in a luminal organ of the gastrointestinaltract can include a first step of advancing an ablation structure 101,into the gastrointestinal tract. In a second step, the ablationstructure 101 is supported with an endoscope 111 within thegastrointestinal tract. In a third step, the ablation structure 101 isdeflected toward a tissue surface 3. In a fourth step, energy can beapplied to the ablation structure 101 to ablate the tissue surface 3.

In another method, the step of advancing an endoscope-supported ablationstructure 101 can include advancing the endoscope 111 into a luminalorgan of the gastrointestinal tract and advancing the ablation structure101 over the endoscope 111. For example, the endoscope 111 can bepositioned relative to an ablation target tissue surface 3 after whichthe ablation structure 101 can be advanced over the outside of theendoscope 111 for ablating the target tissue surface 3.

In a further method, the step of supporting the ablation structure 101with an endoscope 111 includes inserting the endoscope 111 into theablation structure 101 (see for example, FIGS. 2A-2D). In a relatedmethod, the ablation structure 101 is supported by a sheath 103 (seeFIGS. 26-28, 30, 31, 32 and 37) and the step of inserting the endoscope111 into the ablation structure 101 includes inserting the endoscope 111into the sheath 103. In a further related method, the step of insertingthe endoscope 111 into the sheath 103 includes creating an opening inthe sheath 103 (not shown).

In a particular method, a distal portion of a sheath 103 having asmaller outer diameter than a proximal portion of the sheath 103, isadapted to be expanded when an endoscope 111 is inserted into it.

In another method, the step of advancing the ablation structure 101 intothe esophagus includes advancing the ablation structure 101 through achannel of the endoscope 111 from either the endoscopes proximal ordistal end (as discussed below for FIGS. 34A, 35A and 36A). In yetanother method, the step of supporting the ablation structure 101comprises supporting the ablation structure 101 with a channel of theendoscope (see as discussed below for FIGS. 34A, 35A, 36A, 37-39). In afurther method, a deflection structure or deflection member 150 isadvanced through a channel of the endoscope 111 and the step ofdeflecting the ablation structure 101 toward a tissue surface 3 includesdeflecting the ablation structure 101 with the deflection structure ordeflection member 150 (see as discussed below for FIGS. 34A, 34B, 35A,35B, 36A, 36B, 37-39).

As illustrated in FIGS. 34A, 35A, and 36A, variously adapted andconfigured ablation structures 101 can fit within and be conveyedthrough an endoscope internal working channel 211. In each case, theablation structure 101 and accompanying deflection mechanism can beconveyed through the internal working channel 211 in a dimensionallycompacted first configuration that is capable of expansion to a secondradially expanded configuration upon exiting the distal end 110 of theendoscope 111 (For example, see FIGS. 34A, 34B, 35A, 35B, 36A, and 36B).

As shown in FIG. 34B, in one embodiment, the deflection mechanism is aninflation member 105, to which the ablation structure 101 can beintegrated within or mounted/attached to, for example by etching,mounting or bonding. The inflation member 105 can be, for example, acompliant, non-compliant or semi-compliant balloon.

As shown in FIGS. 35B and 35B, in another embodiment, the deflectionmechanism is an expandable member 209 that can expand to a seconddesired arrangement and configuration. As shown in FIG. 35B, theexpandable member 209, can be an expandable stent, frame or cage device,to which an ablation structure 101 is mounted or integrated. Forexample, where the expandable member 209 is a wire cage, the wires canbe a component of a bipolar circuit to provide the ablation structure101 feature. Alternatively, the cage can have a flexible electrodecircuit bonded or can be attached to an outer or inner surface of thecage to provide an ablation structure 101 that is an electrode. As shownin FIG. 36B, the expandable member 209, can be a folded or rolled seriesof hoops including or having an attached ablation structure 101 thatexpands upon exiting the endoscope distal end 110.

As further illustrated in FIGS. 37-39, the ablation structure 101 can besupported with a channel of the endoscope 111. In one embodiment asshown in FIGS. 37-39, an ablation device 100 includes a deflectionmember 150 that supports an attached housing 107 and ablation structure101. As shown in FIG. 39, the endoscope 111 includes an internal workingchannel 211 suitable for advancing or retreating the deflection member150 which is connected to an internal coupling mechanism 215 of theablation device 100. FIGS. 37 and 39 both show a deflection member 150including a bent region of the deflection member 150 in a deployedposition, wherein the deflection member 150 bent region is positionedexternal to the endoscope distal end 110. FIG. 38 shows the deflectionmember 150 in an undeployed position, wherein the deflection member 150bent region is positioned internal to the endoscope 111. The ablationstructure 101 is thus supported with a channel of the endoscope 111 (theinternal working channel 211 of the endoscope 111) by way of thedeflection member 150 and the connected internal coupling mechanism 215of the ablation device 100.

In addition, when the deflection member 150 is advanced or movedproximally or distally within the endoscope internal working channel211, the deflection member 150 is accordingly advanced through a channelof the endoscope 111. In another implementation, as shown in FIG. 42,wherein the deflection mechanism is an inflatable member 105 (shown in adeployed configuration) coupled to an inflation line 113, the inflationline 113 can be disposed within the endoscope internal working channel211. In yet another implementation, both the inflatable member 105 (inan undeployed configuration) and inflation line 113 can be advancedwithin the internal working channel 211 either proximally or distally inrelation to the endoscope 111. Conductive wires 109 can pass through theworking channel (not shown) or outside as shown in FIG. 37.

As shown in FIG. 41, in another implementation the endoscope 111includes an internal working channel 211 suitable for supporting theablation housing 107 and ablation structure 101 which are connected toan internal coupling mechanism 215 of the ablation device 100. As such,the connected ablation structure 101 is supported within a channel ofthe endoscope 111. Additionally as shown in FIG. 41, the housing 107 andablation structure 101 can further be supported by an external region ofthe endoscope 111, wherein the internal coupling mechanism 215 isadapted and configured to position the housing 107 in contact with theexternal region of the endoscope 111. The internal coupling mechanism215 can be cannulated (not shown) to facilitate use of the workingchannel to aspirate and flow in fluids or air.

In another ablation method, an additional step includes moving theablation structure 101 with respect to the endoscope 111 within aluminal organ of the gastrointestinal tract. As illustrated in FIGS. 27,28, 30, 32, and 47, and as discussed below, a sheath 103 of the ablationdevice 100 to which the ablation structure 101 is attached can enablemoving the ablation structure 101 with respect to the endoscope 111.Further, as illustrated in FIGS. 34A, 35A, 36A, 37, 38, 39, and 41, anddiscussed above, an internal working channel 211 of the endoscope 111through which at least a part of the ablation device 100 is disposed canenable moving the ablations structure 101 with respect to the endoscope111.

Referring to FIGS. 11, 31, 42, and 44, in yet another method, the stepof deflecting the ablation structure 101 toward a tissue surface 3includes inflating an inflation member 105 of the ablation device 100within a luminal organ of the gastrointestinal tract. The inflationmember 105 can be arranged and configured to be reversibly inflatable.The inflation member 105 can be inserted along with the ablationstructure 101 into an alimentary tract in a collapsed configuration andexpanded upon localization at a pre-selected treatment area. In oneimplementation, the inflation member 105 is a balloon. For example, inFIGS. 11, 31, 42, and 44 it is shown how deflecting the ablationstructure 101 toward a tissue surface 3 is achieved when the inflationmember 105 is inflated or deployed. As illustrated in FIGS. 11, 31, 42,and 44, upon sufficient inflation, the inflation member 105 contacts atissue surface 3 consequently deflecting the ablation structure 101which contacts an opposing tissue surface 3.

As shown in FIGS. 19B, 20, 35, 36 and discussed above, in a furthermethod, the step of deflecting the ablation structure 101 includesexpanding a deflection structure or deflection member 150. In oneimplementation, as shown in FIG. 19A the ablation device 100 includes asheath 103, wherein the sheath 103 is arranged and configured to receivethe deflection member 150, the endoscope 111 and ablation structure 101internally to the sheath 103. In one implementation, the deflectionmember 150 is a shape memory alloy, for example, Nitinol. The flexibleextensions of the deflection member 150 in this embodiment can becoupled to the endoscope, an elastomeric sheath 115 of the ablationdevice 100 (shown in FIG. 19A) or any part of the device 100, includingthe ablation housing 107.

As shown in FIGS. 34, 35, 36, 37, 38, and 39, and discussed above, in afurther method, the step of deflecting the ablation structure 101includes moving a deflection structure or deflection member 150.

Briefly, in each case moving the deflection 150 is used to change thedeflection member 150 from a non-deployed to a deployed configuration.As shown in FIG. 23, in one embodiment, deflecting the ablationstructure 101 includes a flexing point in the ablation structure 101,wherein the ablation structure 101 can deflect in response to, forexample, resistance met in contacting a tissue surface 3.

As shown in FIGS. 43, 44, and 45A-45C and as discussed in further detailbelow, in another method, the step of deflecting the ablation structure101 includes rotating, pivoting, turning or spinning the ablationstructure 101 with respect to the endoscope 111 along their respectiveand parallel longitudinal axes. Deflection of the ablation structure 101with respect to the endoscope 111 can occur in combination with theendoscope 111 distal end 110 deflecting with respect to a target site onthe wall of an luminal organ of the gastrointestinal tract or without.Also, the ablation structure 101 can deflect in combination with aninflation member 105 used to achieve apposition of the ablation device100 to the tissue. In some embodiments, the step of deflecting theablation structure 101 may additionally include any combination of theabove disclosed deflecting steps.

As shown in FIGS. 19, 20, 21, 22, 34A, 34B, 35A, 35B, 36A, 36B, 46B, and47, in another ablation method, an additional step includes moving theablation structure 101 from a first configuration to a second radiallyexpanded configuration. The details regarding radial expansion of theablation structure 101 shown in FIGS. 19, 20, 21, and 22 are describedbelow, while the details for FIGS. 34A, 34B, 35A, 35B, 36A, and 36B aredescribed above. Additionally, as shown in FIGS. 46B and 47 the ablationstructure 101 can be arranged in a first configuration wherein theablation structure 101 is coupled directly or alternatively through anhousing 107 (not shown) to an inflation member 105B attached to acatheter 254. In an undeployed configuration as shown in FIGS. 46B and47, the non-inflated inflation member 105 and ablation structure 101have a relatively low profile in relation to the endoscope 111. Whendeployed, the inflation member 105 moves the ablation structure 101 to asecond radially expanded configuration (not shown).

As shown in FIGS. 15, 16, 40, 43, 44, 45A-45C, 46B, and 47, in a furthermethod, an additional step includes attaching the ablation structure 101to the endoscope 111. As shown in FIGS. 15 and 16, attachment of theablation structure 101 to the endoscope 111 can also be by way of anelastomeric sheath 115 The elastomeric sheath 115 can removably hold theablation structure 101 in a desired position on the endoscope 111. Theelastomeric sheath 115 can be arranged and configured to fit over theendoscope distal end 110. As shown in FIGS. 15 and 16, the inflationmember 105B can be attached to the elastomeric sheath 115 oralternatively the inflation member 105B can also act as the “elastomericsheath” (not shown).

In another method, the step of attaching the ablation structure 101 tothe endoscope 111 includes attaching the ablation structure 101 to anoutside surface of the endoscope. Alternatively, the attaching step caninclude, for example, attaching to an inside surface, an outside orinside feature of the endoscope, or any combinations of the above.Lubricants such as water, IPA, jelly, or oil may be use to aidattachment and removal of the ablation device from the endoscope.

As shown in FIG. 41, in a further method, the step of attaching theablation structure 101 to the endoscope 111, includes an ablationstructure 101 having an attached rolled sheath 116, wherein attachingthe ablation structure 101 to the endoscope 111 includes unrolling thesheath 116 over an outside surface of the endoscope 111. The rolledsheath 116 can additionally cover the electrical connections 109 of theablation device 100 along a length of the endoscope 111 (see FIG. 41).In a related method, the ablation structure 101 is attached to theendoscope 111 by an attaching step including unrolling the rolled sheath116 over an outside surface of the endoscope 111 and part of theablation structure 101.

In another method, as shown in FIG. 40, the step of attaching theablation structure 101 to the endoscope 111 includes attaching theablation structure 101 to a channel of the endoscope. As shown in FIG.40, in one implementation, the housing 107 and ablation structure 101are coupled to an internal coupling mechanism 215 that can be positionedwithin an internal working channel 211 of the endoscope 111. Theinternal coupling mechanism 215 in FIG. 40 is shown as attached to theinternal working channel 211 at the endoscope distal end 110. In thisembodiment, the housing 107 and ablation structure 101 are shown inalignment with and coupled to an outside surface of the endoscope 111near the distal end 110.

In one method of ablating tissue in the alimentary tract, the tissuesurface 3 can include a first treatment area and activation of theablation structure 101 step can include activation of the ablationstructure 101 to ablate the first treatment area, and further includemoving the ablation structure 101 to a second area without removing theablation structure 101 from the patient and activating the ablationstructure 101 to ablate the second tissue area 3. Moving, in this sense,refers to moving the ablational structure to the locale of a targetsite, and thereafter, further moving of the structure into atherapeutically effected position can be performed variously byinflating a balloon member, or deflection or inflating a deflectionmember, as described in detail elsewhere. For example, where two or moreareas of the tissue surface 3 of a target area in the wall of an organin the gastrointestinal tract can be ablated by directing the ablationstructure 101 to the first target region and then activating theablation structure 101 to ablate the tissue surface 3. Then, withoutremoving the ablation structure 101 from the patient, the ablationstructure 101 can be directed to the second target area in the wall ofan organ for ablation of the appropriate region of the tissue surface 3.

In general, in another aspect, an ablation device 100 is provided thatincludes an ablation structure 101 removably coupled to an endoscopedistal end 110, and a deflection mechanism adapted and configured tomove the ablation structure 101 toward a tissue surface 3 (see forexample, FIGS. 5-19, 22, 22, 27-29, 30-32, 34A, 35A, 36A, 37, 38, 39,42, 44, and 47).

In a related embodiment, the ablation device 100 additionally includesan ablation structure movement mechanism adapted to move the ablationstructure 101 with respect to the endoscope 111. As discussed below andshown in FIGS. 26-28, and 30-32, the ablation structure movementmechanism can be a sheath 103 to which the ablation structure 101 isattached, wherein the sheath 103 is arranged and configured to move theablation structure 101 with respect to an endoscope 111 received withinthe sheath 103. Alternatively, as discussed above and shown in FIGS.34A, 35A, 36A, and 37-39, the ablation structure movement mechanism canbe in the form of an internal coupling mechanism 215 of the ablationstructure 100, wherein the ablation structure is connected to theinternal coupling mechanism 215 and at least a portion of the internalcoupling mechanism 215 is disposed internally to the endoscope.

In another embodiment, the ablation device 100 additionally includes acoupling mechanism designed to fit over an outside surface of anendoscope 111, to couple the ablation structure 101 with the endoscope111. As discussed above, a spiral sheath 104, an elastomeric sheath 115,a rolled sheath 116 and an internal coupling mechanism as shown in FIGS.15, 16, 40, and 41 respectively, are examples of such couplingmechanisms. In a particular embodiment, the coupling mechanism includesa sheath 103 capable of supporting the ablation structure 101. Thesheath 103 can be tubing, a catheter or other suitable elongate members.The sheath 103 can be arranged and configured so that it can be movedindependently of an associated endoscope.

As shown in FIG. 41, in another embodiment, the sheath 103 can bearranged and configured as a rolled sheath 116 that can be unrolled overthe outside surface of the endoscope. In use, a rolled sheath 116connected to the ablation device 100, for example at substantially nearthe proximal end of the housing 107 (from the perspective of an operatorof the device), can be unrolled from such a position and continue to beunrolled toward the proximal end 112 of the endoscope 111 (see FIG. 47).In this way, the rolled sheath 116 can be caused to contact and coverall or a portion of the length of the endoscope 111 (not shown).Additionally, as the rolled sheath 116 is unrolled along the endoscope111, it can sandwich the electrical connections 109 between the rolledsheath 116 and the endoscope 111 (see generally FIG. 41).

In another embodiment, as shown in FIGS. 30 and 31, the sheath 103 canbe arranged and configured to support a deflection mechanism wherein thedeflection mechanism includes a deflection structure or deflectionmember 150. As illustrated in FIGS. 30 and 31, where the deflectionmember 150 is an inflation member 105, the inflation member 105 can bedirectly attached to the sheath 103. As shown in each case, theinflation member 105 is positioned opposite the placement of theablation structure 101, which is also attached to the sheath 103. Thisconfiguration of the sheath 103 provides support for the inflationmember 105 and the ablation structure 101 irrespective of thepositioning of the endoscope distal end 110. For example, as shown inFIG. 30, the endoscope distal end 110 can be positioned to provide a gapbetween the distal end 110 and a distal end of the sheath 103 where theablation structure 101 and inflation member 105 are positioned. Incontrast, as shown in FIG. 31 the endoscope distal end 110 can extendthrough and beyond the distal end of the sheath 103.

In another embodiment, as shown in FIG. 26, the sheath 103 can beelongated. FIG. 26 illustrates a sheath including electrical connections109 and an inflation line 113. The sheath 103 may include pneumaticand/or over extruded wires impregnated within the sheath 103. In use,the sheath 103 can be introduced first into an alimentary tract, whereinthe sheath 103 serves as a catheter like guide for introduction of theendoscope 111 within the sheath 103. Alternatively, the endoscope 111may be introduced first and thereby serve as a guidewire for the sheath103 to be introduced over. FIG. 26 also shows attachment of an inflationmember 105 to the sheath 103, in an arrangement wherein the ablationstructure 101 is attached to the inflation member 105 opposite thesheath 103 attachment point.

In yet another embodiment (not shown) the sheath 103 includes anoptically transmissive portion 158 adapted and configured to cooperatewith a visual channel 161 of an endoscope 111. For example, the sheath103 may be made of clear, translucent or transparent polymeric tubingincluding PVC, acrylic, and Pebax® (a polyether block amide). As shownin FIG. 24, one component of an endoscope 111 can be a visual channel161 that provides visual imaging of a tissue surface 3 as imaged fromthe endoscope distal end 110. For example, the transmissive portion 158can allow visualization of the wall of an esophagus 3 through thetransmissive portion 158 of the sheath 103. As shown in FIG. 28 and inthe cross-section view provided in FIG. 29, the sheaths 103 shown inFIGS. 27 and 28, include an optically transmissive portion 158 arrangedand configured to provide viewing of tissue surfaces 3 through the wallof the sheath 103, with the aid of an internally disposed endoscope 111having a visual channel 161. Also shown in cross-section in FIG. 29 areportions of the sheath 103 through which electrical connections 109 andan inflation line 113 can pass. These features may be imbedded into thesheath 103 inner wall or attached to the sheath 103 inner wall. As shownin FIG. 27, the sheath 103 including a transmissive portion 158 canextend past the endoscope distal tip 110. Alternatively, as shown inFIGS. 27, 28, and 31, the endoscope distal end 110 can extend distallypast the transmissive portion 158 of the sheath 103.

In another implementation, the transmissive portion 158 of the sheath103 can be reinforced structurally with coil or braid elementsincorporated therein to prevent ovalization and/or collapsing of thesheath 103, particularly while deflecting the ablation device 100

In a further embodiment, the sheath 103 includes a slit 203 formed in aproximal portion of the sheath 103, the slit 203 being designed to opento admit an endoscope distal end 110 into the sheath 103. As shown inFIG. 32 the proximal portion of the sheath 103 can include a perforationregion or slit 203. The slit 203 can extend partially of fully along thelength of the sheath 103. The slit 203 enables the sheath 103 to bepulled back, or opened when, for example introducing an endoscope 111into the sheath 103. In one implementation, as shown in FIG. 32, thesheath 103 additionally includes a locking collar 205 for locking thesheath 103 in a desired position in respect to the endoscope 111.

As shown in FIGS. 33A and 33B, the distal portion of the sheath 103 canhave a smaller outer diameter than a, proximal portion of the sheath103, the distal portion of the sheath 103 being adapted and configuredto be expanded when an endoscope 111 is inserted into it (not shown).This embodiment can aid in accessing an endoscope 111 in a case wherethe sheath 103 is advanced first into a target site within thealimentary tract. Since the distal end of the sheath 103 is smaller indiameter, but includes a slit 203, the sheath 103 can accept a largeroutside diameter endoscope 111 because when the endoscope 111 isadvanced, the slit 203 of the sheath 103 allows for widening of thesheath 103.

In general, in another aspect, a method of ablating tissue in within thealimentary tract includes advancing an ablation structure 101 into thealimentary tract while supporting the ablation structure 101 with anendoscope 111. The endoscope distal end 110 can be bent to move theablation structure 101 into contact with a tissue surface followed byactivation of the ablation structure 101 to ablate the tissue surface 3(see e.g., FIG. 43). In a particular embodiment, the ablation structure101 includes a plurality of electrodes and the activating step includesapplying energy to the electrodes.

In general, in another aspect the coupling mechanism is designed to fitover an outside surface of an endoscope 111, to couple the ablationstructure 101 with the endoscope 111, rather than being for example, asheath (as discussed above), and is adapted and configured to provide acertain freedom of movement to the ablation structure 101, including butnot limited to flexing and/or rotating and/or pivoting with respect tothe endoscope 111 when coupled to the endoscope 111. The freedom ofmovement is with respect to one, two, or three axes, thereby providingone, two, or three degrees of freedom. Non-limiting examples of suitablecoupling mechanisms include a flex joint, pin joint, U-joint, balljoint, or any combination thereof. The following described couplingmechanism embodiments advantageously provide for a substantially uniformapposition force between a supporting endoscope 111 and an ablationstructure 101 when localized at a target tissue surface 3.

As shown in FIGS. 43, 44, 45A, and 45B, the coupling mechanism can be aring 250 attached to the housing 107 and the endoscope 111, wherein thehousing 107 is adapted and configured to flex, rotate or pivot about thering 250. For example, as illustrated in FIG. 43 (see detailed view inFIG. 38B), where the ablation device 100 is coupled to a deflectabledistal end 110 of an endoscope 111 by a ring 250, when the device 100 isdeflected toward the tissue surface 3 of the wall of the lumen of agastrointestinal organ, the housing 107 upon contact aligns the ablationstructure 101 with the tissue surface 3 by flexing, rotating or pivotingabout the ring 250 coupling. In these embodiments, the endoscope and thehousing that supports the ablation structure both have their ownlongitudinal axis, and these axes are situated parallel to each other.The coupling mechanism that attaches the housing to the endoscope allowsa pivoting movement between the longitudinal axis of the housing and thelongitudinal axis of the endoscope. Advantageously, sufficient contactpressure provided by deflection of the distal end 110 of the endoscope101 can produce a desired degree of contact between the ablationstructure 101 and the tissue surface 3, irrespective of the precisealignment of the distal end 112 in respect to a plane of the tissuesurface 3 to be treated. For the purposes of this disclosure, a “desireddegree of contact”, “desired contact”, “therapeutic contact”, or“therapeutically effective contact” between the ablation structure 101and the tissue surface 3, includes complete or substantially-completecontact between all or a portion of a predetermined target on the tissuesurface 3 (e.g. a site on the wall of a luminal organ of thegastrointestinal tract) by all or a portion of the ablation structure101.

As shown in FIG. 44, in a different yet related embodiment, where thedeflection mechanism of the ablation device 100 is an inflatable member105, a ring 250 coupling allows for flexing, rotating or pivoting of thehousing 107 and ablation structure 101. As in the previous case,sufficient contact pressure provided through deflection, here by theinflatable member 105, can produce a desired degree of contact betweenthe ablation structure 101 and the tissue surface 3. Again,advantageously, the desired contact can be achieved irrespective of theprecise alignment of the deflected endoscope 111 distal end 110 inrespect to a plane of the tissue surface 3 to be treated, because of theflexing, rotating or pivoting provided by the ring 250 coupling.

As shown in FIG. 45A, in a related embodiment, the coupling mechanismbetween the ablation device 100 and an endoscope 111 can be an elasticband 252, wherein the housing 107 of the device 100 is flexibly coupledto the elastic band 252. For example, as illustrated in FIG. 45C, wherethe ablation device 100 is coupled to a distal end 110 of an endoscope111 by an elastic band 252, when the device 100 is deflected toward atissue surface 3 of the wall of a luminal organ of the gastrointestinaltract, alignment between the housing 107 and accordingly the ablationstructure 101 and the tissue surface 3, can be achieved by flexing aboutthe elastic band 252 coupling. Once more, advantageously, the desiredcontact can be achieved irrespective of the precise alignment of thedeflected endoscope's 111 distal end 110 in respect to a plane of thetissue surface 3 to be treated, because of the flexing capabilityprovided by the elastic band 252 coupling.

As shown in FIG. 45A, in another related embodiment, the couplingmechanism between the ablation device 100 and an endoscope 111 can be acombination of a ring 250 and an elastic band 252, wherein the housing107 of the device 100 is coupled to the elastic band 252. For example,as illustrated in FIG. 45A, where the ablation device 100 is coupled toa distal end 110 of an endoscope 111 by an elastic band 252, when thedevice 100 is deflected toward a tissue surface 3 of, for example, thewall of a luminal organ of the gastrointestinal tract (not shown),alignment between the housing 107 and accordingly the ablation structure101, and the tissue surface 3 by flexing, rotating or pivoting about thering 250 and the elastic band 252 coupling can be achieved. Again,advantageously, the desired contact can be achieved irrespective of theprecise alignment of the deflected endoscope 111 distal end 110 inrespect to a plane of the tissue surface 3 to be treated, because of theflexing rotating or pivoting provided by the elastic band 252 coupling.

In another embodiment, the ablation device 100 additionally includes analternative coupling mechanism between the ablation device 100 and anendoscope 111 that is arranged and configured to fit within a channel ofan endoscope 111. The coupling mechanism can be an internal couplingmechanism 215 and can be configured and arranged to couple the ablationstructure 101 within an internal working channel 211 of an endoscope 111(see FIG. 37 and as discussed above).

As shown in FIGS. 34A, 34B, 35A, 35B, 36A, and 36B, in one embodiment ofsuch a coupling mechanism, the ablation structure 101 is adapted andconfigured to fit within the endoscope internal working channel 211.Additionally, as shown in FIGS. 34A, 34B, 35A, 35B, 36A, and 36B, in arelated embodiment, the deflection mechanism is also adapted andconfigured to fit within the endoscope internal working channel 211.

In each of the embodiments described above and shown in FIGS. 34A, 34B,35A, 35B, 36A, and 36B, after expansion of the inflatable member 105 orexpandable member 209 and subsequent treatment of a target tissue 3, thecoupling means can further serve as a means to draw, pull or retrievethe ablation structure 101 and deflection mechanism back into theendoscope internal working channel 211. Furthermore, in addition toproviding coupling of the ablation structure 101 with the endoscopeinternal working channel 112, the coupling mechanism can includeelectrical connections 109 to provide energy to the ablation structure101.

In a related embodiment, again wherein the ablation device 100additionally includes a coupling mechanism adapted and configured to fitwithin a channel of an endoscope 111, the coupling mechanism can includea shape memory member and the deflection mechanism can include a bentportion of the shape memory member. As shown in FIGS. 37-39, thecoupling mechanism can be an internal coupling mechanism 215. As shown,the internal coupling mechanism 215 can be disposed within an endoscopeinternal working channel 211 and extend beyond the endoscope distal end100. Additionally, the internal coupling mechanism 215 can be connectedto a deflection mechanism that is a deflection member 150. Thedeflection member 150 can include a bent portion and can be connected tothe housing 107. As shown in FIG. 38 and discussed above, the bentportion of the deflection member 150 can be disposed within theendoscope internal working channel 211, causing the ablation structure101 to move into a non-deployed position. Upon advancing the internalcoupling mechanism 215 toward the endoscope distal end 110, the shapememory nature of the deflection member 150 facilitates deployment of theablation structure 101 to a position suitable for ablation.

In general, in one aspect, the ablation structure 101 of the ablationdevice 100 includes an optically transmissive portion 158 adapted andconfigured to cooperate with a visual channel of an endoscope 111. Asshown in FIGS. 27-31 and discussed above, the optically transmissiveportion 158 can be a sheath 103 of the ablation device 100.

In one embodiment, the ablation structure 101 of the ablation device 100is further adapted and configured to move from a first configuration toa second radially expanded configuration. As shown in FIGS. 19-22, theablation structure 101 and housing 107 can be designed to reversiblymove from a first less radially expanded configuration (see FIGS. 20 and21) to a second radially expanded configuration useful for ablation.Foldable or deflectable configurations that provide for reversibleradial expansion of the housing 107 and the ablation structure 101 canfacilitate access to tissue surfaces because of reduced size.Additionally, foldable or deflectable configurations are helpful inregard to cleaning, introduction, retrieval, and repositioning of thedevice in the luminal organs of the gastrointestinal tract.

The ablation device 100 shown in FIGS. 19 and 20 includes an ablationstructure actuator 152 arranged and configured to move the ablationstructure 101 from the first configuration (see FIG. 20) to a secondradially-expanded configuration (see FIG. 21). As shown in FIGS. 19 and20, the actuator 152 can be elongate and designed to work with areceiver 154 arranged and configured to receive the actuator 152. Theactuator 152 can be a wire, rod or other suitable elongate structure.Alternatively, the actuator 152 can be a hydraulic actuation means withor without a balloon component. In a particular embodiment, the actuator152 is a stiffening wire.

As illustrated in FIG. 20, before the actuator 152 is disposed withinthe portion of receiver 154 attached to the housing 107, both thehousing 107 and the ablation structure 101 are in a first positionhaving a first configuration. As illustrated in FIG. 21, after theactuator 152 is partially or fully introduced into the receiver 154, thehousing 107 and the ablation structure 101 are consequently changed to asecond radially expanded configuration relative to the firstconfiguration. Introduction of the actuator 152 into the receiver 154can force the portions of the housing 107 and ablation structure 101flanking the receiver 154 to expand radially (see FIG. 19). In oneembodiment, the housing 107 is heat set in a flexed first configurationsuitable for positioning the ablation device 100 near a target tissuesurface 3. After a target tissue surface 3 has been reached, theactuator 152 can be introduced into the receiver 154 to achieve thesecond radially expanded configuration which is useful for ablation ofthe tissue surface 3.

In a related alternative embodiment, the housing 107 and ablationstructure 101 include an unconstrained shape that is radially expandedand includes one or more flex points to allow for collapsed or reducedradial expansion when positioned distally to the distal end 110 of anendoscope 111 and compressed by an elastomeric sheath 115 (not shown).

As shown in FIGS. 21 and 22, in another embodiment, the ablationstructure 101 of the ablation device 100 is adapted and configured tomove from a first configuration to a second radially expandedconfiguration wherein the ablation device 100 further includes anexpandable member 156. As illustrated in FIG. 19, the expandable member156 can be positioned between the housing 107 and the endoscope 111,where in unexpanded form, the ablation structure 101 is accordinglyconfigured in a first configuration. Upon expansion of the expandablemember 156, the ablation structure 101 configuration is changed to asecond radially expanded configuration (see FIG. 20).

In one embodiment, the deflection mechanism of the ablation device 100includes an inflatable inflation member 105. As shown in FIGS. 11, 21,22, 25B, 27, 28, 30, 31, 34A, 34B, 42, 44, 46, and 47 and discussedabove, the inflation member 105 can facilitate deflection of the device100 in relation to a tissue surface 3.

In another embodiment, the deflection mechanism includes an expandablemember 156 (see FIGS. 35B and 36B, discussed in detail above). As shownin FIG. 35B, the expandable member 209, can be an expandable stent,frame or cage device. As shown in FIG. 36B, the expandable member 209,can be an expanded series of connected hoops that can be folded orrolled prior to expansion.

In another advantageous embodiment, the ablation device 100 furthercomprises a torque transmission member adapted and configured totransmit torque from a proximal end of the endoscope 111 to the ablationstructure 101 to rotate the ablation structure 101 about a central axisof the endoscope 111. In a particular embodiment, the torquetransmission member includes first and second interlocking membersadapted to resist relative movement between the endoscope 111 and theablation structure 101 about the central axis. As shown in FIGS. 46 and47, in one embodiment the first interlocking member is a key 258 and thesecond interlocking member is a keyway 256. In one embodiment, the firstinterlocking member is attached to a sheath 103 surrounding theendoscope 111 and the second interlocking member is attached to acatheter 254 supporting the ablation structure 101. For example, asshown in FIGS. 46B, 46C, and 47, the key 258 can be attached to a sheath103 surrounding the endoscope 111 and the keyway 256 can be attached toa catheter 254 supporting the ablation structure 101. In a furtherrelated embodiment, the catheter 254 and sheath 103 are arranged andconfigured for relative movement along the central axis of the endoscope111. The sheath 103 can be, for example, an elastomeric sheath whereinthe key 258 is attached to the outside of the sheath 103 substantiallyalong a longitudinal axis of the sheath 103 (see FIG. 46C). In use, thisembodiment provides for a 1-to-1 torque transmission of the ablationdevice 100 endoscope assembly 111 when the endoscope proximal end 112 ismanipulated, while also providing for positioning of the ablationstructure 101 either proximal or distal to the endoscope distal end 110in situ. Additionally, the sheath 103 can be pre-loaded into thecatheter 254 or loaded separately.

In general, in one aspect, an ablation device 100 is provided includingan ablation structure 101, and a coupling mechanism adapted to removablycouple the ablation structure 101 to a distal end 110 of an endoscope111 and to permit the ablation structure 101 to rotate and/or pivot withrespect to the endoscope when coupled to the endoscope. Various relatedembodiments wherein, for example, the coupling mechanism comprises aring 250 and the ablation structure 101 is adapted to rotate and/orpivot about the ring 250; wherein the coupling mechanism comprises anelastic band 252 adapted to flex to permit the ablation structure 101 torotate and/or pivot; wherein the ablation device 100 further includes adeflection mechanism adapted and configured to move the ablationstructure 101 toward a tissue surface 3; and, wherein such a deflectionmechanism includes an inflatable member, have been set out in detailabove.

While most embodiments described herein have made use of radiofrequencyenergy as an exemplary ablational energy, and consequently have made useof electrodes as an energy transmitting element, it should be understoodthat these examples are not limiting with regard to energy source andenergy delivery or transmitting elements. As also described herein,other forms of energy, as well as cryoablating approaches, may providefor ablation of target areas in such a manner that ablation isfractional or partial, as described herein, where some portions oftarget area tissue are ablated, and some portions of target area tissueare not substantially ablated.

Terms and Conventions

Unless defined otherwise, all technical terms used herein have the samemeanings as commonly understood by one of ordinary skill in the art ofablational technologies and treatment for metabolic conditions anddiseases such as obesity, metabolic syndrome, and diabetes mellitus.Specific methods, devices, and materials are described in thisapplication, but any methods and materials similar or equivalent tothose described herein can be used in the practice of the presentinvention. While embodiments of the invention have been described insome detail and by way of exemplary illustrations, such illustration isfor purposes of clarity of understanding only, and is not intended to belimiting. Various terms have been used in the description to convey anunderstanding of the invention; it will be understood that the meaningof these various terms extends to common linguistic or grammaticalvariations or forms thereof. It will also be understood that whenterminology referring to devices, equipment, or drugs that have beenreferred to by trade names, brand names, or common names, that theseterms or names are provided as contemporary examples, and the inventionis not limited by such literal scope. Terminology that is introduced ata later date that may be reasonably understood as a derivative of acontemporary term or designating of a hierarchal subset embraced by acontemporary term will be understood as having been described by the nowcontemporary terminology. Further, while some theoretical considerationshave been advanced in furtherance of providing an understanding of, forexample, the biology of metabolic disease, or the mechanisms of actionof therapeutic ablation, the claims to the invention are not bound bysuch theory. Moreover, any one or more features of any embodiment of theinvention can be combined with any one or more other features of anyother embodiment of the invention, without departing from the scope ofthe invention. Still further, it should be understood that the inventionis not limited to the embodiments that have been set forth for purposesof exemplification, but is to be defined only by a fair reading ofclaims that are appended to the patent application, including the fullrange of equivalency to which each element thereof is entitled.

What is claimed is:
 1. A method of ablationally-treating tissue at atarget area in a gastrointestinal tract of a patient with apathophysiological metabolic condition comprising: delivering energyfrom an ablation structure to a tissue surface within the target area,the target area being a portion of the gastrointestinal tract thatincludes at least a portion of a jejunum; and controlling the deliveryof energy to the tissue surface within the target area and into a depthof tissue within the target area to treat the pathophysiologicalmetabolic condition.
 2. The method of claim 1 wherein controlling thedelivery of energy into depth of the tissue includes controlling thedelivery of energy inwardly from the tissue surface such that sufficientenergy to achieve ablation is delivered to some layers and insufficientenergy is delivered to other layers to achieve ablation.
 3. The methodof claim 1 wherein controlling the delivery of energy to the tissuesurface within the target area includes delivering sufficient energy toachieve ablation in one portion of the tissue target area to achieveablation and delivering insufficient energy to another portion of thesurface to achieve ablation.
 4. The method of claim 3 wherein deliveringsufficient energy to achieve ablation includes configuring an electrodepattern such that some spacing between electrodes is sufficiently closeto allow conveyance of a level of energy sufficient to ablate and otherspacing between electrodes is insufficiently close to allow conveyanceof the level of energy sufficient to ablate.
 5. The method of claim 3wherein delivering sufficient energy to achieve ablation includesoperating an electrode pattern such that the energy delivered betweensome electrodes is sufficient to ablate and energy sufficient to ablateis not delivered between some electrodes.
 6. The method of claim 1wherein controlling the delivery of energy into inwardly from thesurface of the tissue consists of ablating some portion of tissue withinthe epithelial layer.
 7. The method of claim 1 wherein controlling thedelivery of energy into inwardly from the surface of the tissue consistsof ablating some portion of tissue within the epithelial layer and thelamina propria.
 8. The method of claim 1 wherein controlling thedelivery of energy into inwardly from the surface of the tissue consistsof ablating some portion of tissue within the epithelial layer, thelamina propria, and the muscularis mucosae.
 9. The method of claim 1wherein controlling the delivery of energy into inwardly from thesurface of the tissue consists of ablating some portion of tissue withinthe epithelial layer, the lamina propria, the muscularis mucosae, andthe submucosa.
 10. The method of claim 1 wherein controlling thedelivery of energy into inwardly from the surface of the tissue consistsof ablating some portion of tissue within the epithelial layer, thelamina propria, the muscularis mucosae, the submucosa, and themuscularis propria.
 11. The method of claim 1 wherein thepathophysiological metabolic condition includes any one or more of type2 diabetes, insulin resistance, obesity, or metabolic syndrome.
 12. Themethod of claim 1 further comprising restoring the pathophysiologicalmetabolic condition of the patient toward a normal metabolic condition.13. The method of claim 12 wherein restoring the metabolic conditiontoward a normal metabolic condition includes any of decreasing bloodglucose levels, decreasing blood insulin levels, decreasing insulinresistance, decreasing body weight, or decreasing body mass index. 14.The method of claim 1 wherein the ablation target area includes cellsthat support the secretion of insulin in the patient, and wherein uponreceiving transmitted energy from the ablation structure are rendered atleast partially dysfunctional.
 15. The method of claim 14 wherein thecells supporting the effect of insulin are endocrine cells.
 16. Themethod of claim 14 wherein the cells supporting the effect of insulinare nerve cells.
 17. The method of claim 1 wherein the ablation targetarea includes cells that support the response of the patient to insulin,and wherein upon receiving transmitted energy from the ablationstructure are rendered at least partially dysfunctional.
 18. The methodof claim 17 wherein supporting the response to insulin includes any ofpromoting the greater effectiveness of secreted insulin or decreasingthe effect of agents that have an anti-insulin effect.
 19. The method ofclaim 17 wherein the cells supporting the effect of insulin areendocrine cells.
 20. The method of claim 17 wherein the cells supportingthe effect of insulin are nerve cells.
 21. The method of claim 1 whereinthe target area is located in the gastric antrum.
 22. The method ofclaim 1 wherein the target area is located in the pylorus.
 23. Themethod of claim 1 wherein controlling the delivery of energy across thetissue surface within the target area and into the depth of tissuewithin the target area allows achievement of a partial ablation intissue layers of the gastrointestinal tract.
 24. The method of claim 23wherein the target area is in the epithelial layer of the gastricantrum.
 25. The method of claim 23 wherein the target area is inepithelial layer of the any of the duodenum or jejunum.
 26. The methodof claim 23 wherein partial ablation in the epithelial layer slows therate of nutrient absorption through the epithelial layer.
 27. The methodof claim 23 wherein the target area includes the muscularis of thegastric antrum causing a slowing of gastric emptying.
 28. The method ofclaim 23 wherein the target area includes the muscularis of the pyloriscausing a slowing of gastric emptying.
 29. The method of claim 23wherein the target area includes the muscularis of the duodenum causinga slowing of gastric emptying.
 30. The method of claim 1 wherein theablation has a permanent effect on the function of the target area. 31.The method of claim 1 wherein the ablation has a transient effect on thefunction of the target area.
 32. The method of claim 31 wherein thetransient effect has duration that ranges from a period of about one dayto about one year.
 33. The method of claim 31 wherein during the timewhen the function of the target region is transiently affected, themethod further includes evaluating the patient for a beneficialtherapeutic effect of the ablation.
 34. The method of claim 33 whereinin the event of a beneficial therapeutic effect, the method furtherincludes repeating the ablation of the target region.
 35. The method ofclaim 34 wherein the repeated ablation is a transient ablation.
 36. Themethod of claim 34 wherein the repeated ablation is a permanentablation.
 37. The method of claim 1 wherein the electrode pattern isconfigured circumferentially through 360 degrees around the ablationstructure.
 38. The method of claim 37 wherein transmitting energy fromthe ablation structure includes transmitting energy asymmetricallythrough the 360 degree circumference such that ablation is focusedwithin an arc of less than 360 degrees.
 39. The method of claim 1wherein the electrode pattern is configured circumferentially through anarc of less than 360 degrees around the ablation structure.
 40. Themethod of claim 1 further comprising evaluating the target area at apoint in time after the delivering energy step to determine the statusof the area.
 41. The method of claim 40 wherein the evaluating stepoccurs in close time proximity after the delivery of energy, to evaluatethe immediate post-treatment status of the site.
 42. The method of claim40 wherein the evaluating step occurs at least one day after thedelivery of energy.
 43. The method of claim 1 wherein the deliveringenergy step is performed more than once.
 44. The method of claim 1further compromising deriving energy for transmitting from an energysource that is controlled by a control system.
 45. The method of claim44 wherein the energy source is a generator.
 46. The method of claim 44further comprising feedback controlling the energy transmission so as toprovide any of a specific power, power density, energy, energy density,circuit impedance, or tissue temperature.
 47. The method of claim 1wherein the energy comprises at least radiofrequency energy or steamheat.
 48. The method of claim 1 wherein, the target area being a portionof the gastrointestinal tract that includes at least a portion of aduodenum.